run_metadata: 33805
This data as json
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| 33805 | SRR30670312 | SRX26088984 | SRS22655387 | SRP532815 | PRJNA1161406 | Epigenetic regulation by Polycomb Repressive Complex 1 promotes Cerebral Cavernous Malformations | GSE277234 | Transcriptome Analysis | Cerebral cavernous malformations CCMs are anomalies that develop mainly in the cerebral vasculature. They result from mutations in CCM1/KRIT1 CCM2 or CCM3/PDCD10. Loss of CCM proteins triggers a MAPK Krüppel like factor 2 KLF2 signaling cascade which induces a pathophysiological pattern of gene expression within endothelial cells. The downstream target genes that are activated by KLF2 are mostly unknown. Here we show that Chromobox Protein Homolog 7 CBX7 component of the Polycomb Repressive Complex 1 contributes to pathophysiological KLF2 signaling during zebrafish cardiovascular development. CBX7/cbx7a mRNA is strongly upregulated in lesions of CCM patients and in human mouse and zebrafish CCM deficient endothelial cells. The silencing or pharmacological inhibition of CBX7/Cbx7a suppresses pathological CCM phenotypes in ccm2 zebrafish CCM2 deficient HUVECs and in a pre clinical murine CCM3 disease model. Whole transcriptome datasets from zebrafish cardiovascular tissues and human endothelial cells reveal that CBX7/Cbx7a plays a role in the activation of KLF2 targets including genes encoding TEK Angiopoietin1 WNT9 and endoMT proteins. Our findings uncover an intricate interplay in the regulation of Klf2 dependent biomechanical signaling by CBX7 in CCM. This work also provides insights for therapeutic strategies in the pathogenesis of CCM. Overall design: In this experiment we want to compare the RNA transcripts of different genetic background of zebrafish heart which is considerred as enriched endothelial tissue. We have pooled heart samples from 56 hpf 59 hpf hour zebrafish embryos with 3 conditions 4 groups: wildtype wt ccm2 mutant ccm2 double knockout mutant DKOwBF. We prepared 4 biological samples for each group. Each sample consisting of 15 60 heart was RNA extracted DNase treatment using Zymo Quick RNA Microprep Kit. RNA later was checked integrity and concentration by D1000 Agilent ScreenTape. Samples with RIN values ranged from 7.2 9.3 were further librarized with NebNext Ultra II kit with 30 ng of RNA as starting point. | pubmed:39402138 | DKOwBF 4 | GSM8516797 | source name:heart|tissue:heart|cell type:enriched endothelial cells|genotype:ccm2m201;cbx7apbb62|geo loc name:missing|collection date:missing | DKOwBF 4 | base calling alignment filtering peak calling generation of normalized counts has been done by staff of sequecing facility using usegalaxy.eu platform Assembly: GRCz10 Supplementary files format and content: bigwig file includes raw count for each sample | heart | RNA extraction DNase treatment was done using Zymo Quick RNA Microprep Kit. RNA later was checked integrity and concentration by D1000 Agilent ScreenTape. Samples with RIN values ranged from 7.2 9.3 were further librarized with 30ng of RNA as starting point. RNA library was prepared using NebNext Ultra II kit following manufacturer's protocol | 2 dpf zebrafish embryo | tissue:heart|cell type:enriched endothelial cells|genotype:ccm2m201;cbx7apbb62 | GSM8516797 | GSM8516797: DKOwBF 4; Danio rerio; RNA Seq | GSM8516797 r1 | GSM8516797 | 1 | RNA extraction DNase treatment was done using Zymo Quick RNA Microprep Kit. RNA later was checked integrity and concentration by D1000 Agilent ScreenTape. Samples with RIN values ranged from 7.2 9.3 were further librarized with 30ng of RNA as starting point. RNA library was prepared using NebNext Ultra II kit following manufacturer's protocol | RNA-Seq | TRANSCRIPTOMIC | cDNA | PAIRED | ILLUMINA | NextSeq 550 | SRP532815 | DKOwBF_4_R1_val_1.fq.gz DKOwBF_4_R2_val_2.fq.gz | fastq fastq | 2631656843.0 | 35135298.0 | GSM8516797 r1 | 0:37.47 1:37.43 | A:693207862;C:610024232;G:611701090;T:716593105;N:130554 | 37 | 37 | 693207862 | 610024232 | 611701090 | 716593105 | 130554 | SRX26088984 | SRS22655387 | SRA1972600 | University of Potsdam | University of Potsdam | B | B | biological fallback assumption | illumina | nextseq | full_length | random_priming | nebnext | bulk | unknown | unknown | Germany | 2024-09-15 | Hatching | Embryo | Heart | Cardiovascular System |