rowid,run.accession,experiment.accession,sample.accession,study.accession,bioproject,study.title,study.alias,study.type,study.abstract,study.attributes,study.PMIDs,sample.description,sample.title,sample.alias,sample.centername,sample.attributes,GEOsample.title,GEOsample.dataprocessing,GEOsample.source,GEOsample.treatmentprotocol,GEOsample.extractprotocol,GEOsample.growthprotocol,GEOsample.characteristics,GEOsample.accession,experiment.title,experiment.alias,experiment.library_name,experiment.design_description,experiment.library_construction_protocol,experiment.attributes,experiment.library_strategy,experiment.library_source,experiment.library_selection,experiment.library_layout,experiment.platform,experiment.instrument_model,experiment.spot_descriptor,experiment.study_ref,run.title,run.attributes,run.filename,run.semantic_name,run.total_bases,run.total_spots,run.alias,run.read_lengths,run.base_counts,run.r1_length,run.r2_length,run.r3_length,run.r4_length,run.Acount,run.Ccount,run.Gcount,run.Tcount,run.Ncount,run.experiment,run.pool_member,submission.accession,submission.srasource,submission.bioprojectsource,seqdetective.n_mates,seqdetective.mapping_rate.mate1,seqdetective.mapping_rate.mate2,seqdetective.nofeature_rate.mate1,seqdetective.nofeature_rate.mate2,seqdetective.sparsity.mate1,seqdetective.sparsity.mate2,seqdetective.pos_strand_rate.mate1,seqdetective.pos_strand_rate.mate2,seqdetective.readlen.mate1,seqdetective.readlen.mate2,seqdetective.judgement.mate1,seqdetective.judgement.mate2,seqdetective.judgement.reason,platform_family,instrument_generation,read_bias,selection_class,prep_kit,sc_or_bulk,tech_class,technology,tech_variant,submission.bioprojectsource.country,earliest_date,devstage_curation,devstage_curation_coarse,tissue_curation,tissue_curation_coarse 10383,ERR8517249,ERX8083723,ERS10517669,ERP135370,PRJEB50765,HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS,69e2093b-755e-4be3-88b8-5b4a761258fe,Other,A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA which is dependent on its subcellular localization and on RNA recognition and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue we discovered an increased nuclear translocation but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2 a downstream target of HNRNPK involved in DNA damage response. Finally we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response opening novel therapeutic strategies for C9 ALS/FTD.,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,PUBMED:29302778;PUBMED:35895140,Modifier control,hnRNPK 003,SAMEA12918519,vib-ku leuven,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918519|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:hnRNPK 003|common name:zebrafish|sample name:hnRNPK 003,,,,,,,,,NextSeq 500 paired end sequencing; Raw reads: hnRNPK 003,webin reads hnRNPK 003,,unspecified,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,NextSeq 500,,ERP135370,Raw reads: hnRNPK 003,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,hnRNPK_003_R1.fastq.gz hnRNPK_003_R2.fastq.gz,fastq fastq,2931486932.0,19421721.0,webin reads hnRNPK 003,0:75.51 1:75.43,A:759548162;C:700272829;G:700149526;T:770783019;N:733396,75,75,,,759548162,700272829,700149526,770783019,733396,ERX8083723,ERS10517669,ERA8937191,vib-ku leuven|European Nucleotide Archive,vib-ku leuven,2,0.9621,0.96378,0.06994,0.06876,0.68757,0.68998,0.46746,0.47041,76,75,B,B,biological fallback assumption,illumina,nextseq,unknown,poly_a,unknown,bulk,unknown,unknown,,Belgium,2022-08-22,Undetermined,Undetermined,Undetermined,Undetermined 10384,ERR8517226,ERX8083700,ERS10517665,ERP135370,PRJEB50765,HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS,69e2093b-755e-4be3-88b8-5b4a761258fe,Other,A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA which is dependent on its subcellular localization and on RNA recognition and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue we discovered an increased nuclear translocation but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2 a downstream target of HNRNPK involved in DNA damage response. Finally we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response opening novel therapeutic strategies for C9 ALS/FTD.,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,PUBMED:29302778;PUBMED:35895140,Modifier control,hnRNPK 001,SAMEA12918515,vib-ku leuven,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918515|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:hnRNPK 001|common name:zebrafish|sample name:hnRNPK 001,,,,,,,,,NextSeq 500 paired end sequencing; Raw reads: hnRNPK 001,webin reads hnRNPK 001,,unspecified,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,NextSeq 500,,ERP135370,Raw reads: hnRNPK 001,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,hnRNPK_001_R1.fastq.gz hnRNPK_001_R2.fastq.gz,fastq fastq,2728299749.0,18074835.0,webin reads hnRNPK 001,0:75.51 1:75.43,A:710869412;C:649804308;G:644363972;T:722599378;N:662679,75,75,,,710869412,649804308,644363972,722599378,662679,ERX8083700,ERS10517665,ERA8936710,vib-ku leuven|European Nucleotide Archive,vib-ku leuven,2,0.96092,0.96336,0.07296,0.07144,0.68862,0.69209,0.47036,0.47104,76,76,B,B,biological fallback assumption,illumina,nextseq,unknown,poly_a,unknown,bulk,unknown,unknown,,Belgium,2022-08-22,Undetermined,Undetermined,Undetermined,Undetermined 10385,ERR8517194,ERX8083668,ERS10517668,ERP135370,PRJEB50765,HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS,69e2093b-755e-4be3-88b8-5b4a761258fe,Other,A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA which is dependent on its subcellular localization and on RNA recognition and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue we discovered an increased nuclear translocation but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2 a downstream target of HNRNPK involved in DNA damage response. Finally we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response opening novel therapeutic strategies for C9 ALS/FTD.,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,PUBMED:29302778;PUBMED:35895140,RNA control,GFP 003,SAMEA12918518,vib-ku leuven,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918518|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:GFP 003|common name:zebrafish|sample name:GFP 003,,,,,,,,,NextSeq 500 paired end sequencing; Raw reads: GFP 003,webin reads GFP 003,,unspecified,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,NextSeq 500,,ERP135370,Raw reads: GFP 003,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,GFP_003_R1.fastq.gz GFP_003_R2.fastq.gz,fastq fastq,2845571506.0,18850866.0,webin reads GFP 003,0:75.52 1:75.43,A:737412560;C:678774596;G:684567775;T:744108157;N:708418,75,75,,,737412560,678774596,684567775,744108157,708418,ERX8083668,ERS10517668,ERA8936242,vib-ku leuven|European Nucleotide Archive,vib-ku leuven,2,0.96279,0.96355,0.06774,0.06607,0.68864,0.69183,0.469,0.46906,76,76,B,B,biological fallback assumption,illumina,nextseq,unknown,poly_a,unknown,bulk,unknown,unknown,,Belgium,2022-08-22,Undetermined,Undetermined,Undetermined,Undetermined 10386,ERR8517159,ERX8083633,ERS10517664,ERP135370,PRJEB50765,HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS,69e2093b-755e-4be3-88b8-5b4a761258fe,Other,A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA which is dependent on its subcellular localization and on RNA recognition and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue we discovered an increased nuclear translocation but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2 a downstream target of HNRNPK involved in DNA damage response. Finally we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response opening novel therapeutic strategies for C9 ALS/FTD.,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,PUBMED:29302778;PUBMED:35895140,RNA control,GFP 001,SAMEA12918514,vib-ku leuven,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918514|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:GFP 001|common name:zebrafish|sample name:GFP 001,,,,,,,,,NextSeq 500 paired end sequencing; Raw reads: GFP 001,webin reads GFP 001,,unspecified,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,NextSeq 500,,ERP135370,Raw reads: GFP 001,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,GFP_001_R1.fastq.gz GFP_001_R2.fastq.gz,fastq fastq,2873485447.0,19035162.0,webin reads GFP 001,0:75.52 1:75.44,A:746120172;C:687054955;G:682142981;T:757435799;N:731540,75,75,,,746120172,687054955,682142981,757435799,731540,ERX8083633,ERS10517664,ERA8935703,vib-ku leuven|European Nucleotide Archive,vib-ku leuven,2,0.96176,0.96461,0.07014,0.06932,0.68672,0.68913,0.47006,0.46794,75,76,B,B,biological fallback assumption,illumina,nextseq,unknown,poly_a,unknown,bulk,unknown,unknown,,Belgium,2022-08-22,Undetermined,Undetermined,Undetermined,Undetermined 10387,ERR8517115,ERX8083589,ERS10517671,ERP135370,PRJEB50765,HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS,69e2093b-755e-4be3-88b8-5b4a761258fe,Other,A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA which is dependent on its subcellular localization and on RNA recognition and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue we discovered an increased nuclear translocation but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2 a downstream target of HNRNPK involved in DNA damage response. Finally we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response opening novel therapeutic strategies for C9 ALS/FTD.,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,PUBMED:29302778;PUBMED:35895140,Modifier rescue,91S hnRNPK 003,SAMEA12918521,vib-ku leuven,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918521|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:91S hnRNPK 003|common name:zebrafish|sample name:91S hnRNPK 003,,,,,,,,,NextSeq 500 paired end sequencing; Raw reads: 91S hnRNPK 003,webin reads 91S hnRNPK 003,,unspecified,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,NextSeq 500,,ERP135370,Raw reads: 91S hnRNPK 003,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,91S_hnRNPK_003_R1.fastq.gz 91S_hnRNPK_003_R2.fastq.gz,fastq fastq,2853403405.0,18902398.0,webin reads 91S hnRNPK 003,0:75.52 1:75.44,A:739541111;C:681340573;G:681790014;T:750013318;N:718389,75,75,,,739541111,681340573,681790014,750013318,718389,ERX8083589,ERS10517671,ERA8935191,vib-ku leuven|European Nucleotide Archive,vib-ku leuven,2,0.96234,0.96429,0.0679,0.06627,0.68984,0.69126,0.46434,0.47087,76,76,B,B,biological fallback assumption,illumina,nextseq,unknown,poly_a,unknown,bulk,unknown,unknown,,Belgium,2022-08-22,Undetermined,Undetermined,Undetermined,Undetermined 10388,ERR8517082,ERX8083556,ERS10517667,ERP135370,PRJEB50765,HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS,69e2093b-755e-4be3-88b8-5b4a761258fe,Other,A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA which is dependent on its subcellular localization and on RNA recognition and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue we discovered an increased nuclear translocation but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2 a downstream target of HNRNPK involved in DNA damage response. Finally we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response opening novel therapeutic strategies for C9 ALS/FTD.,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,PUBMED:29302778;PUBMED:35895140,Modifier rescue,91S hnRNPK 001,SAMEA12918517,vib-ku leuven,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918517|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:91S hnRNPK 001|common name:zebrafish|sample name:91S hnRNPK 001,,,,,,,,,NextSeq 500 paired end sequencing; Raw reads: 91S hnRNPK 001,webin reads 91S hnRNPK 001,,unspecified,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,NextSeq 500,,ERP135370,Raw reads: 91S hnRNPK 001,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,91S_hnRNPK_001_R1.fastq.gz 91S_hnRNPK_001_R2.fastq.gz,fastq fastq,2795603091.0,18519699.0,webin reads 91S hnRNPK 001,0:75.52 1:75.43,A:722724564;C:672552332;G:664566386;T:735058575;N:701234,75,75,,,722724564,672552332,664566386,735058575,701234,ERX8083556,ERS10517667,ERA8934579,vib-ku leuven|European Nucleotide Archive,vib-ku leuven,2,0.96307,0.96547,0.06551,0.06458,0.68714,0.68856,0.46817,0.46555,76,76,B,B,biological fallback assumption,illumina,nextseq,unknown,poly_a,unknown,bulk,unknown,unknown,,Belgium,2022-08-22,Undetermined,Undetermined,Undetermined,Undetermined 10389,ERR8517039,ERX8083513,ERS10517670,ERP135370,PRJEB50765,HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS,69e2093b-755e-4be3-88b8-5b4a761258fe,Other,A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA which is dependent on its subcellular localization and on RNA recognition and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue we discovered an increased nuclear translocation but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2 a downstream target of HNRNPK involved in DNA damage response. Finally we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response opening novel therapeutic strategies for C9 ALS/FTD.,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,PUBMED:29302778;PUBMED:35895140,Toxic condition,91S GFP 003,SAMEA12918520,vib-ku leuven,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918520|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:91S GFP 003|common name:zebrafish|sample name:91S GFP 003,,,,,,,,,NextSeq 500 paired end sequencing; Raw reads: 91S GFP 003,webin reads 91S GFP 003,,unspecified,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,NextSeq 500,,ERP135370,Raw reads: 91S GFP 003,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,91S_GFP_003_R1.fastq.gz 91S_GFP_003_R2.fastq.gz,fastq fastq,2946600193.0,19521826.0,webin reads 91S GFP 003,0:75.51 1:75.43,A:763284580;C:704439363;G:702989767;T:775149110;N:737373,75,75,,,763284580,704439363,702989767,775149110,737373,ERX8083513,ERS10517670,ERA8933888,vib-ku leuven|European Nucleotide Archive,vib-ku leuven,2,0.96151,0.96295,0.06621,0.06481,0.68807,0.69092,0.46928,0.46982,75,76,B,B,biological fallback assumption,illumina,nextseq,unknown,poly_a,unknown,bulk,unknown,unknown,,Belgium,2022-08-22,Undetermined,Undetermined,Undetermined,Undetermined 10390,ERR8516998,ERX8083472,ERS10517666,ERP135370,PRJEB50765,HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS,69e2093b-755e-4be3-88b8-5b4a761258fe,Other,A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA which is dependent on its subcellular localization and on RNA recognition and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue we discovered an increased nuclear translocation but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2 a downstream target of HNRNPK involved in DNA damage response. Finally we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response opening novel therapeutic strategies for C9 ALS/FTD.,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,PUBMED:29302778;PUBMED:35895140,Toxic condition,91S GFP 001,SAMEA12918516,vib-ku leuven,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918516|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:91S GFP 001|common name:zebrafish|sample name:91S GFP 001,,,,,,,,,NextSeq 500 paired end sequencing; Raw reads: 91S GFP 001,webin reads 91S GFP 001,,unspecified,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,NextSeq 500,,ERP135370,Raw reads: 91S GFP 001,ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22,91S_GFP_001_R1.fastq.gz 91S_GFP_001_R2.fastq.gz,fastq fastq,2821113913.0,18686946.0,webin reads 91S GFP 001,0:75.52 1:75.44,A:726676187;C:676899384;G:676400816;T:740427303;N:710223,75,75,,,726676187,676899384,676400816,740427303,710223,ERX8083472,ERS10517666,ERA8933211,vib-ku leuven|European Nucleotide Archive,vib-ku leuven,2,0.96147,0.96465,0.07106,0.06991,0.68822,0.69556,0.47261,0.47451,75,76,B,B,biological fallback assumption,illumina,nextseq,unknown,poly_a,unknown,bulk,unknown,unknown,,Belgium,2022-08-22,Undetermined,Undetermined,Undetermined,Undetermined 31986,SRR28894021,SRX24452441,SRS21206092,SRP505663,PRJNA1107798,liver,PRJNA1107798,Other,wt and elovl2 mutant liver,,,,,elovl2 4,,strain:elovl2 4|isolate:not collected|breed:not collected|cultivar:not collected|ecotype:not collected|age:not collected|dev stage:not collected|collection date:not collected|geo loc name:not collected|sex:male|tissue:liver|BioSampleModel:Model organism or animal,,,,,,,,,elovl2 4,8,8,liver,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,SINGLE,ILLUMINA,Illumina HiSeq X,,SRP505663,,,elovl2-4,fastq,4367010000.0,29113400.0,elovl2 4.gz,0:150,A:1161921878;C:1015107709;G:1012841192;T:1177020487;N:118734,150,,,,1161921878,1015107709,1012841192,1177020487,118734,SRX24452441,SRS21206092,SRA1858809,Chinese Academy of Sciences (CAS)|The Institute of Hydrobiology,Chinese Academy of Sciences (CAS),,,,,,,,,,,,B,,usable mapping rate,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,China,2024-05-04,Undetermined,Undetermined,Liver,Liver and Biliary System 31987,SRR28894022,SRX24452440,SRS21206091,SRP505663,PRJNA1107798,liver,PRJNA1107798,Other,wt and elovl2 mutant liver,,,,,elovl2 3,,strain:elovl2 3|isolate:not collected|breed:not collected|cultivar:not collected|ecotype:not collected|age:not collected|dev stage:not collected|collection date:not collected|geo loc name:not collected|sex:male|tissue:liver|BioSampleModel:Model organism or animal,,,,,,,,,elovl2 3,7,7,liver,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,SINGLE,ILLUMINA,Illumina HiSeq X,,SRP505663,,,elovl2-3,fastq,5125533150.0,34170221.0,elovl2 3.gz,0:150,A:1365645170;C:1189846405;G:1184721703;T:1385180096;N:139776,150,,,,1365645170,1189846405,1184721703,1385180096,139776,SRX24452440,SRS21206091,SRA1858809,Chinese Academy of Sciences (CAS)|The Institute of Hydrobiology,Chinese Academy of Sciences (CAS),,,,,,,,,,,,B,,usable mapping rate,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,China,2024-05-04,Undetermined,Undetermined,Liver,Liver and Biliary System 31988,SRR28894023,SRX24452439,SRS21206090,SRP505663,PRJNA1107798,liver,PRJNA1107798,Other,wt and elovl2 mutant liver,,,,,elovl2 2,,strain:elovl2 2|isolate:not collected|breed:not collected|cultivar:not collected|ecotype:not collected|age:not collected|dev stage:not collected|collection date:not collected|geo loc name:not collected|sex:male|tissue:liver|BioSampleModel:Model organism or animal,,,,,,,,,elovl2 2,6,6,liver,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,SINGLE,ILLUMINA,Illumina HiSeq X,,SRP505663,,,elovl2-2,fastq,3261375750.0,21742505.0,elovl2 2.gz,0:150,A:878478836;C:747963062;G:743760185;T:891083235;N:90432,150,,,,878478836,747963062,743760185,891083235,90432,SRX24452439,SRS21206090,SRA1858809,Chinese Academy of Sciences (CAS)|The Institute of Hydrobiology,Chinese Academy of Sciences (CAS),,,,,,,,,,,,B,,usable mapping rate,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,China,2024-05-04,Undetermined,Undetermined,Liver,Liver and Biliary System 31989,SRR28894024,SRX24452438,SRS21206089,SRP505663,PRJNA1107798,liver,PRJNA1107798,Other,wt and elovl2 mutant liver,,,,,elovl2 1,,strain:elovl2 1|isolate:not collected|breed:not collected|cultivar:not collected|ecotype:not collected|age:not collected|dev stage:not collected|collection date:not collected|geo loc name:not collected|sex:male|tissue:liver|BioSampleModel:Model organism or animal,,,,,,,,,elovl2 1,5,5,liver,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,SINGLE,ILLUMINA,Illumina HiSeq X,,SRP505663,,,elovl2-1,fastq,3629422950.0,24196153.0,elovl2 1.gz,0:150,A:974034477;C:836070594;G:831068189;T:988151010;N:98680,150,,,,974034477,836070594,831068189,988151010,98680,SRX24452438,SRS21206089,SRA1858809,Chinese Academy of Sciences (CAS)|The Institute of Hydrobiology,Chinese Academy of Sciences (CAS),,,,,,,,,,,,B,,usable mapping rate,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,China,2024-05-04,Undetermined,Undetermined,Liver,Liver and Biliary System 31990,SRR28894025,SRX24452437,SRS21206088,SRP505663,PRJNA1107798,liver,PRJNA1107798,Other,wt and elovl2 mutant liver,,,,,WT 4,,strain:WT 4|isolate:not collected|breed:not collected|cultivar:not collected|ecotype:not collected|age:not collected|dev stage:not collected|collection date:not collected|geo loc name:not collected|sex:male|tissue:liver|BioSampleModel:Model organism or animal,,,,,,,,,WT 4,4,4,liver,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,SINGLE,ILLUMINA,Illumina HiSeq X,,SRP505663,,,WT-4,fastq,4037472900.0,26916486.0,WT 4.gz,0:150,A:1083383010;C:932278459;G:925831402;T:1095868616;N:111413,150,,,,1083383010,932278459,925831402,1095868616,111413,SRX24452437,SRS21206088,SRA1858809,Chinese Academy of Sciences (CAS)|The Institute of Hydrobiology,Chinese Academy of Sciences (CAS),,,,,,,,,,,,B,,usable mapping rate,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,China,2024-05-04,Undetermined,Undetermined,Liver,Liver and Biliary System 31991,SRR28894026,SRX24452436,SRS21206087,SRP505663,PRJNA1107798,liver,PRJNA1107798,Other,wt and elovl2 mutant liver,,,,,WT 3,,strain:WT 3|isolate:not collected|breed:not collected|cultivar:not collected|ecotype:not collected|age:not collected|dev stage:not collected|collection date:not collected|geo loc name:not collected|sex:male|tissue:liver|BioSampleModel:Model organism or animal,,,,,,,,,WT 3,3,3,liver,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,SINGLE,ILLUMINA,Illumina HiSeq X,,SRP505663,,,WT-3,fastq,3651994200.0,24346628.0,WT 3.gz,0:150,A:978819903;C:844506880;G:836704943;T:991863415;N:99059,150,,,,978819903,844506880,836704943,991863415,99059,SRX24452436,SRS21206087,SRA1858809,Chinese Academy of Sciences (CAS)|The Institute of Hydrobiology,Chinese Academy of Sciences (CAS),,,,,,,,,,,,B,,usable mapping rate,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,China,2024-05-04,Undetermined,Undetermined,Liver,Liver and Biliary System 31992,SRR28894027,SRX24452435,SRS21206086,SRP505663,PRJNA1107798,liver,PRJNA1107798,Other,wt and elovl2 mutant liver,,,,,WT 2,,strain:WT 2|isolate:not collected|breed:not collected|cultivar:not collected|ecotype:not collected|age:not collected|dev stage:not collected|collection date:not collected|geo loc name:not collected|sex:male|tissue:liver|BioSampleModel:Model organism or animal,,,,,,,,,WT 2,2,2,liver,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,SINGLE,ILLUMINA,Illumina HiSeq X,,SRP505663,,,WT-2,fastq,3845338950.0,25635593.0,WT 2.gz,0:150,A:1033991995;C:885977441;G:878907105;T:1046356459;N:105950,150,,,,1033991995,885977441,878907105,1046356459,105950,SRX24452435,SRS21206086,SRA1858809,Chinese Academy of Sciences (CAS)|The Institute of Hydrobiology,Chinese Academy of Sciences (CAS),,,,,,,,,,,,B,,usable mapping rate,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,China,2024-05-04,Undetermined,Undetermined,Liver,Liver and Biliary System 31993,SRR28894028,SRX24452434,SRS21206085,SRP505663,PRJNA1107798,liver,PRJNA1107798,Other,wt and elovl2 mutant liver,,,,,WT 1,,strain:WT 1|isolate:not collected|breed:not collected|cultivar:not collected|ecotype:not collected|age:not collected|dev stage:not collected|collection date:not collected|geo loc name:not collected|sex:male|tissue:liver|BioSampleModel:Model organism or animal,,,,,,,,,WT 1,1,1,liver,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,SINGLE,ILLUMINA,Illumina HiSeq X,,SRP505663,,,WT-1,fastq,3756883050.0,25045887.0,WT 1.gz,0:150,A:1005244721;C:868304979;G:865360007;T:1017811504;N:161839,150,,,,1005244721,868304979,865360007,1017811504,161839,SRX24452434,SRS21206085,SRA1858809,Chinese Academy of Sciences (CAS)|The Institute of Hydrobiology,Chinese Academy of Sciences (CAS),,,,,,,,,,,,B,,usable mapping rate,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,China,2024-05-04,Undetermined,Undetermined,Liver,Liver and Biliary System 47613,SRR6760977,SRX3733411,SRS2990508,SRP133266,PRJNA434353,Transcriptome assemblies 10 vertebrate species,PRJNA434353,Other,2 types of content: a Raw RNA seq files from cell lines of 10 vertebrate species human mouse cow tasmanian devil chicken duck zebra finch xenopus medaka and zebrafish 4 replicates per species. b Refined transcriptomes post combining with paired proteomics data and data curation.,,,4 replicates,,Zebrafish,,strain:not applicable|isolate:not applicable|breed:not applicable|cultivar:not applicable|ecotype:not applicable|age:not applicable|dev stage:not applicable|sex:missing|tissue:scale|cell line:BRF41|cell type:fibroblast|BioSampleModel:Model organism or animal,,,,,,,,,Transcriptome assemblies 10 vertebrate species,zebrafish replicate2,zebrafish replicate2,Zebrafish sample replicate 2,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina HiSeq 2500,,SRP133266,,,Sample_imb_butter_2014_04_30_zebrafish_B_R2.fastq.gz Sample_imb_butter_2014_04_30_zebrafish_B_R1.fastq.gz,fastq fastq,8021078014.0,39708307.0,Sample imb butter 2014 04 30 zebrafish B R2.fastq.gz,0:101 1:101,A:2198831905;C:1810184353;G:1779924959;T:2210094554;N:22042243,101,101,,,2198831905,1810184353,1779924959,2210094554,22042243,SRX3733411,SRS2990508,SRA660975,Institute of Molecular Biology|Quantitative Proteomics,Institute of Molecular Biology,2,0.94194,0.93911,0.07724,0.08406,0.75724,0.75558,0.47712,0.49049,101,101,B,B,biological fallback assumption,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Unknown,2019-02-15,Undetermined,Undetermined,Scale,Surface Structure 47614,SRR6760978,SRX3733410,SRS2990508,SRP133266,PRJNA434353,Transcriptome assemblies 10 vertebrate species,PRJNA434353,Other,2 types of content: a Raw RNA seq files from cell lines of 10 vertebrate species human mouse cow tasmanian devil chicken duck zebra finch xenopus medaka and zebrafish 4 replicates per species. b Refined transcriptomes post combining with paired proteomics data and data curation.,,,4 replicates,,Zebrafish,,strain:not applicable|isolate:not applicable|breed:not applicable|cultivar:not applicable|ecotype:not applicable|age:not applicable|dev stage:not applicable|sex:missing|tissue:scale|cell line:BRF41|cell type:fibroblast|BioSampleModel:Model organism or animal,,,,,,,,,Transcriptome assemblies 10 vertebrate species,zebrafish replicate1,zebrafish replicate1,Zebrafish sample replicate 1,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina HiSeq 2500,,SRP133266,,,Sample_imb_butter_2014_04_29_zebrafish_A_R1.fastq.gz Sample_imb_butter_2014_04_29_zebrafish_A_R2.fastq.gz,fastq fastq,7117920864.0,35237232.0,Sample imb butter 2014 04 29 zebrafish A R2.fastq.gz,0:101 1:101,A:1980152632;C:1580333689;G:1558362064;T:1979596193;N:19476286,101,101,,,1980152632,1580333689,1558362064,1979596193,19476286,SRX3733410,SRS2990508,SRA660975,Institute of Molecular Biology|Quantitative Proteomics,Institute of Molecular Biology,2,0.9342,0.93044,0.08741,0.09642,0.75674,0.75497,0.49192,0.46492,101,101,B,B,biological fallback assumption,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Unknown,2018-02-22,Undetermined,Undetermined,Scale,Surface Structure 47615,SRR6760981,SRX3733407,SRS2990508,SRP133266,PRJNA434353,Transcriptome assemblies 10 vertebrate species,PRJNA434353,Other,2 types of content: a Raw RNA seq files from cell lines of 10 vertebrate species human mouse cow tasmanian devil chicken duck zebra finch xenopus medaka and zebrafish 4 replicates per species. b Refined transcriptomes post combining with paired proteomics data and data curation.,,,4 replicates,,Zebrafish,,strain:not applicable|isolate:not applicable|breed:not applicable|cultivar:not applicable|ecotype:not applicable|age:not applicable|dev stage:not applicable|sex:missing|tissue:scale|cell line:BRF41|cell type:fibroblast|BioSampleModel:Model organism or animal,,,,,,,,,Transcriptome assemblies 10 vertebrate species,zebrafish replicate4,zebrafish replicate4,Zebrafish sample replicate 4,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina HiSeq 2500,,SRP133266,,,Sample_imb_butter_2014_04_32_zebrafish_D_R1.fastq.gz Sample_imb_butter_2014_04_32_zebrafish_D_R2.fastq.gz,fastq fastq,8570683654.0,42429127.0,Sample imb butter 2014 04 32 zebrafish D R1.fastq.gz,0:101 1:101,A:2343151377;C:1943560489;G:1909682494;T:2350658549;N:23630745,101,101,,,2343151377,1943560489,1909682494,2350658549,23630745,SRX3733407,SRS2990508,SRA660975,Institute of Molecular Biology|Quantitative Proteomics,Institute of Molecular Biology,2,0.94036,0.94349,0.0838,0.0779,0.75538,0.75737,0.4881,0.48296,101,101,B,B,biological fallback assumption,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Unknown,2019-02-15,Undetermined,Undetermined,Scale,Surface Structure 47616,SRR6760982,SRX3733406,SRS2990508,SRP133266,PRJNA434353,Transcriptome assemblies 10 vertebrate species,PRJNA434353,Other,2 types of content: a Raw RNA seq files from cell lines of 10 vertebrate species human mouse cow tasmanian devil chicken duck zebra finch xenopus medaka and zebrafish 4 replicates per species. b Refined transcriptomes post combining with paired proteomics data and data curation.,,,4 replicates,,Zebrafish,,strain:not applicable|isolate:not applicable|breed:not applicable|cultivar:not applicable|ecotype:not applicable|age:not applicable|dev stage:not applicable|sex:missing|tissue:scale|cell line:BRF41|cell type:fibroblast|BioSampleModel:Model organism or animal,,,,,,,,,Transcriptome assemblies 10 vertebrate species,zebrafish replicate3,zebrafish replicate3,Zebrafish sample replicate 3,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina HiSeq 2500,,SRP133266,,,Sample_imb_butter_2014_04_31_zebrafish_C_R1.fastq.gz Sample_imb_butter_2014_04_31_zebrafish_C_R2.fastq.gz,fastq fastq,5889796416.0,29157408.0,Sample imb butter 2014 04 31 zebrafish C R1.fastq.gz,0:101 1:101,A:1629550499;C:1313886355;G:1293890602;T:1636478119;N:15990841,101,101,,,1629550499,1313886355,1293890602,1636478119,15990841,SRX3733406,SRS2990508,SRA660975,Institute of Molecular Biology|Quantitative Proteomics,Institute of Molecular Biology,2,0.93285,0.93628,0.09745,0.0871,0.7586,0.7611,0.47374,0.47763,101,101,B,B,biological fallback assumption,illumina,hiseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Unknown,2018-02-22,Undetermined,Undetermined,Scale,Surface Structure 68886,SRR18218068,SRX14364510,SRS12177805,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,WKM CG1 1,,strain:CG1|age:not collected|sex:not collected|tissue:whole kidney marrow|birth date: |death date:16 07 2019|genotype:Wild type|biological replicate:WKM CG1 biological replicate 1|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio whole kidney marrow CG1,WKM CG1 1,WKM CG1 1,CG1 WT zebrafish were sacrificed to harvest the whole kidney marrow WKM for further analysis. The RNA was extracted from WKM cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAAARAAPEI-P1A1_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAAARAAPEI-P1A1_2.fq.gz,fastq fastq,18015161100.0,60050537.0,FCHT5GHDSXX L1 HKRDZEBmfpEAAARAAPEI P1A1 1.fq.gz,0:150 1:150,A:4626900295;C:4400273225;G:4421661364;T:4566300408;N:25808,150,150,,,4626900295,4400273225,4421661364,4566300408,25808,SRX14364510,SRS12177805,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.94715,0.94844,0.03897,0.03893,0.72176,0.72182,0.51658,0.50581,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Kidney,Renal System 68889,SRR18218067,SRX14364507,SRS12177802,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,Thy rag2 RFP 6,,strain:Tu/AB|age:not collected|sex:not collected|tissue:thymus|birth date: |death date:02 07 2019|genotype:rag2:RFP|biological replicate:Thy rag2 RFP biological replicate 4|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio thymus Tu/AB,Thy rag2 RFP 6,Thy rag2 RFP 6,Tu/AB WT zebrafish were sacrificed to harvest the thymus visible through RFP staining for further analysis. The RNA was extracted from sorted thymic cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAAPRABPEI-P86H2_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAAPRABPEI-P86H2_2.fq.gz,fastq fastq,18061636200.0,60205454.0,FCHT5GHDSXX L1 HKRDZEBmfpEAAPRABPEI P86H2 1.fq.gz,0:150 1:150,A:4749806271;C:4292116510;G:4365562558;T:4654124713;N:26148,150,150,,,4749806271,4292116510,4365562558,4654124713,26148,SRX14364507,SRS12177802,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.9283,0.92884,0.11636,0.1154,0.77642,0.77697,0.48938,0.49117,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Thymus,Hematopoietic System 68890,SRR18218069,SRX14364506,SRS12177801,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,Thy rag2 RFP 5,,strain:Tu/AB|age:not collected|sex:not collected|tissue:thymus|birth date: |death date:02 07 2019|genotype:rag2:RFP|biological replicate:Thy rag2 RFP biological replicate 3|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio thymus Tu/AB,Thy rag2 RFP 5,Thy rag2 RFP 5,Tu/AB WT zebrafish were sacrificed to harvest the thymus visible through RFP staining for further analysis. The RNA was extracted from sorted thymic cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAAORAAPEI-P74G2_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAAORAAPEI-P74G2_2.fq.gz,fastq fastq,16916167800.0,56387226.0,FCHT5GHDSXX L1 HKRDZEBmfpEAAORAAPEI P74G2 1.fq.gz,0:150 1:150,A:4469149097;C:4004191756;G:4070955203;T:4371847041;N:24703,150,150,,,4469149097,4004191756,4070955203,4371847041,24703,SRX14364506,SRS12177801,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.92644,0.92786,0.13071,0.13011,0.77833,0.77792,0.47942,0.4816,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Thymus,Hematopoietic System 68891,SRR18218070,SRX14364505,SRS12177800,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,Thy rag2 RFP 4,,strain:Tu/AB|age:not collected|sex:not collected|tissue:thymus|birth date: |death date:02 07 2019|genotype:rag2:RFP|biological replicate:Thy rag2 RFP biological replicate 2|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio thymus Tu/AB,Thy rag2 RFP 4,Thy rag2 RFP 4,Tu/AB WT zebrafish were sacrificed to harvest the thymus visible through RFP staining for further analysis. The RNA was extracted from sorted thymic cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAANRABPEI-P62F2_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAANRABPEI-P62F2_2.fq.gz,fastq fastq,17996947500.0,59989825.0,FCHT5GHDSXX L1 HKRDZEBmfpEAANRABPEI P62F2 1.fq.gz,0:150 1:150,A:4882125302;C:4136332786;G:4194970590;T:4783492952;N:25870,150,150,,,4882125302,4136332786,4194970590,4783492952,25870,SRX14364505,SRS12177800,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.86095,0.86165,0.25113,0.2504,0.80204,0.80188,0.48309,0.48627,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Thymus,Hematopoietic System 68892,SRR18218071,SRX14364504,SRS12177799,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,Thy rag2 RFP 3,,strain:Tu/AB|age:not collected|sex:not collected|tissue:thymus|birth date: |death date:02 07 2019|genotype:rag2:RFP|biological replicate:Thy rag2 RFP biological replicate 1|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio thymus Tu/AB,Thy rag2 RFP 3,Thy rag2 RFP 3,Tu/AB WT zebrafish were sacrificed to harvest the thymus visible through RFP staining for further analysis. The RNA was extracted from sorted thymic cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAAMRABPEI-P50E2_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAAMRABPEI-P50E2_2.fq.gz,fastq fastq,18041602200.0,60138674.0,FCHT5GHDSXX L1 HKRDZEBmfpEAAMRABPEI P50E2 1.fq.gz,0:150 1:150,A:4726391295;C:4303349397;G:4380843440;T:4630991494;N:26574,150,150,,,4726391295,4303349397,4380843440,4630991494,26574,SRX14364504,SRS12177799,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.93138,0.9316,0.11291,0.11196,0.78143,0.78261,0.4799,0.47958,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Thymus,Hematopoietic System 68906,SRR18218085,SRX14364490,SRS12177785,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,WKM CG1 5,,strain:CG1|age:not collected|sex:not collected|tissue:whole kidney marrow|birth date: |death date:16 07 2019|genotype:Wild type|biological replicate:WKM CG1 biological replicate 5|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio whole kidney marrow CG1,WKM CG1 5,WKM CG1 5,CG1 WT zebrafish were sacrificed to harvest the whole kidney marrow WKM for further analysis. The RNA was extracted from WKM cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAAERABPEI-P49E1_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAAERABPEI-P49E1_2.fq.gz,fastq fastq,18184234500.0,60614115.0,FCHT5GHDSXX L1 HKRDZEBmfpEAAERABPEI P49E1 1.fq.gz,0:150 1:150,A:4903189861;C:4188361342;G:4259034739;T:4833623925;N:24633,150,150,,,4903189861,4188361342,4259034739,4833623925,24633,SRX14364490,SRS12177785,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.93501,0.93633,0.05446,0.05438,0.71583,0.71368,0.5862,0.56886,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Kidney,Renal System 68907,SRR18218087,SRX14364489,SRS12177784,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,WKM CG1 4,,strain:CG1|age:not collected|sex:not collected|tissue:whole kidney marrow|birth date: |death date:16 07 2019|genotype:Wild type|biological replicate:WKM CG1 biological replicate 4|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio whole kidney marrow CG1,WKM CG1 4,WKM CG1 4,CG1 WT zebrafish were sacrificed to harvest the whole kidney marrow WKM for further analysis. The RNA was extracted from WKM cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAADRAAPEI-P37D1_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAADRAAPEI-P37D1_2.fq.gz,fastq fastq,18145210500.0,60484035.0,FCHT5GHDSXX L1 HKRDZEBmfpEAADRAAPEI P37D1 1.fq.gz,0:150 1:150,A:4734947807;C:4358845691;G:4370947434;T:4680443888;N:25680,150,150,,,4734947807,4358845691,4370947434,4680443888,25680,SRX14364489,SRS12177784,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.93212,0.93296,0.05289,0.05244,0.71433,0.71465,0.5085,0.49253,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Kidney,Renal System 68908,SRR18218088,SRX14364488,SRS12177783,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,WKM CG1 3,,strain:CG1|age:not collected|sex:not collected|tissue:whole kidney marrow|birth date: |death date:16 07 2019|genotype:Wild type|biological replicate:WKM CG1 biological replicate 3|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio whole kidney marrow CG1,WKM CG1 3,WKM CG1 3,CG1 WT zebrafish were sacrificed to harvest the whole kidney marrow WKM for further analysis. The RNA was extracted from WKM cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAACRAAPEI-P25C1_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAACRAAPEI-P25C1_2.fq.gz,fastq fastq,18002689500.0,60008965.0,FCHT5GHDSXX L1 HKRDZEBmfpEAACRAAPEI P25C1 1.fq.gz,0:150 1:150,A:4624819223;C:4407791489;G:4420933608;T:4549119250;N:25930,150,150,,,4624819223,4407791489,4420933608,4549119250,25930,SRX14364488,SRS12177783,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.94795,0.94827,0.03817,0.03816,0.72991,0.72987,0.49707,0.49202,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Kidney,Renal System 68909,SRR18218089,SRX14364487,SRS12177782,SRP362416,PRJNA812715,Mutant IL7R collaborates with MYC to induce T cell Acute Lymphoblastic Leukemia,PRJNA812715,Other,T cell acute lymphoblastic leukemia T ALL is an aggressive pediatric cancer. Amongst the wide array of driver mutations 10% of T ALL patients display gain of function mutations in the IL 7 receptor alpha chain IL 7Ralpha encoded by IL7R which occur in different molecular subtypes of this disease. However it is still unclear whether IL 7R mutational activation is sufficient to transform T cell precursors. Also which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here we demonstrate that mutant IL7R alone is capable of inducing T ALL with long latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally we find that mutant IL7R collaborates with Myc to induce early onset T ALL in transgenic zebrafish. T ALLs co expressing mutant IL7R and Myc show activation of STAT5 and AKT pathways harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T ALLs expressing Myc alone. Moreover limiting dilution cell transplantation experiments reveal that activated IL 7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.,,,,,WKM CG1 2,,strain:CG1|age:not collected|sex:not collected|tissue:whole kidney marrow|birth date: |death date:16 07 2019|genotype:Wild type|biological replicate:WKM CG1 biological replicate 2|BioSampleModel:Model organism or animal,,,,,,,,,RNA seq of Danio rerio whole kidney marrow CG1,WKM CG1 2,WKM CG1 2,CG1 WT zebrafish were sacrificed to harvest the whole kidney marrow WKM for further analysis. The RNA was extracted from WKM cells using the RNeasy Mini Kit according to the manufacturers instructions Qiagen. mRNA was enriched using magnetic beads with Oligo dT fragmented and converted to cDNA size selected and PCR amplified generating paired end 100 bp sequences using a Illumina NovaSeq 6000.,,,RNA-Seq,TRANSCRIPTOMIC,PolyA,PAIRED,ILLUMINA,Illumina NovaSeq 6000,,SRP362416,,,FCHT5GHDSXX_L1_HKRDZEBmfpEAABRAAPEI-P13B1_1.fq.gz FCHT5GHDSXX_L1_HKRDZEBmfpEAABRAAPEI-P13B1_2.fq.gz,fastq fastq,18005451300.0,60018171.0,FCHT5GHDSXX L1 HKRDZEBmfpEAABRAAPEI P13B1 1.fq.gz,0:150 1:150,A:4630108478;C:4397001180;G:4413434449;T:4564880633;N:26560,150,150,,,4630108478,4397001180,4413434449,4564880633,26560,SRX14364487,SRS12177782,SRA1380603,Instituto de Medicina Molecular Joao Lobo Antunes|JBarata lab,Instituto de Medicina Molecular Joao Lobo Antunes,2,0.95098,0.95069,0.0373,0.03685,0.72312,0.72301,0.51708,0.51873,150,150,B,B,biological fallback assumption,illumina,novaseq_era,unknown,poly_a,unknown,bulk,unknown,unknown,,Portugal,2022-03-04,Undetermined,Undetermined,Kidney,Renal System