run_metadata: 61419
This data as json
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| 61419 | SRR12712228 | SRX9191118 | SRS7427090 | SRP285378 | PRJNA665656 | The RNA helicase Ddx21 controls Vegfc driven developmental lymphangiogenesis by balancing endothelial cell ribosome biogenesis and p53 p21 signalling [zebrafish] | GSE158566 | Transcriptome Analysis | The development of a differentiated and functional vasculature requires coordinated control of cell fate specification lineage differentiation and vascular network growth. Cellular proliferation is spatiotemporally regulated in developing vessel networks but how this is achieved and differentially controlled in specific lineages is unknown. Using a zebrafish forward genetic screen for mutants that form blood vessels but fail to form lymphatic vessels we uncovered a mutant for the RNA helicase Ddx21. Ddx21 cell autonomously regulates the early development of lymphatic endothelial cells. Ddx21 is essential for Vegfc Vegfr3 driven endothelial cell proliferation. Ddx21 is an established regulator of ribosomal RNA transcription and in the absence of Ddx21 mutant lymphatic endothelial cells show reduced ribosome biogenesis. Ultimately loss of Ddx21 leads to a p53 p21 dependent cell cycle arrest that blocks embryonic lymphangiogenesis. Thus the RNA helicase Ddx21 coordinates the endothelial cell proliferative response to Vegfc Vegfr3 signalling by balancing ribosome biogenesis and p53 p21 signalling. This mechanism may have therapeutic potential in diseases of excessive lymphangiogenesis such as in cancer metastasis or lymphatic malformation. Overall design: LEC and VEC RNA profiles on sibling and ddx21 mutant cells obtained from zebrafish embryos | parent bioproject:PRJNA748172 | ddx21 mutant 04 | GSM4802986 | tissue:ddx21 mutant|genotype/variation:ddx21 mutant|abbreviatedname:Mut 04|cell type:venous and lymphatic ECs VECs LECs | ddx21 mutant 04 | Sequenced reads were assessed for quality using fastqc and aligned and summarized using Subread V2.0.0 functions align and featureCount with default settings Filtering and normalisation of tag counts performed in edgeR using sequential functions filterByExpr calcNormFactors and cpm A batch effect was removed in edgeR using removeBatchEffect function For plotting and differential expression analysis an offset of +1.0 and log2 transformation was applied Genome build: GRCz11 GCA 000002035.4 Supplementary files format and content: Matrix table with normalised batch corredted and log2 transformed CPM for every gene and every sample | ddx21 mutant | At 3 dpf double positve cells were sorted from Tgfli1a:nEGFP;Tg5.2lyve1b:DsRed to isolate LECs and VECs RNA libraries were prepared for sequencing using standard Illumina protocols | genotype/variation:ddx21 mutant|abbreviatedname:Mut 04|cell type:venous and lymphatic ECs VECs LECs | GSM4802986 | GSM4802986: ddx21 mutant 04; Danio rerio; RNA Seq | GSM4802986 | 1 | At 3 dpf double positve cells were sorted from Tgfli1a:nEGFP;Tg5.2lyve1b:DsRed to isolate LECs and VECs RNA libraries were prepared for sequencing using standard Illumina protocols | GEO Accession:GSM4802986 | RNA-Seq | TRANSCRIPTOMIC | cDNA | SINGLE | ILLUMINA | Illumina HiSeq 2000 | SRP285378 | 7-DDX1_mutant4_S2_R1_001.fastq | fastq | 4934798895.0 | 65454382.0 | GSM4802986 r1 | 0:75.39 1:0 | A:1386796418;C:1074595432;G:1108772428;T:1364575960;N:58657 | 75 | 0 | 1386796418 | 1074595432 | 1108772428 | 1364575960 | 58657 | SRX9191118 | SRS7427090 | SRA1131557 | GEO | Hogan Laboratory, Program in Organogenesis and Cancer, Peter MacCallum Cancer Centre | 1 | 0.93352 | 0.1274 | 0.75276 | 0.49744 | 76 | B | usable mapping rate | illumina | hiseq_era | unknown | cdna_unspecified | unknown | bulk | unknown | unknown | Australia | 2020-09-25 | Larval | Larval | Lymphatic System | Cardiovascular System |