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Abstract: TH-PO699

Gene Expression Profile of Pkd1 Null Endothelial Cells During Embryonic Development

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic


  • Outeda, Patricia, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Bai, Hanwen, Vertex Pharmaceuticals, Inc., Boston, Massachusetts, United States
  • Mancini, Joseph A., Vertex Pharmaceuticals, Inc., Boston, Massachusetts, United States
  • Menezes, Luis F., National Institutes of Health, Bethesda, Maryland, United States
  • Watnick, Terry J., University of Maryland School of Medicine, Baltimore, Maryland, United States

Polycystins (PCs) play a critical role in vascular development. Pkd1/2 null embryos die in mid gestation with polyhydramnios, subcutaneous edema and focal hemorrhage. A subset of these phenotypes are recapitulated by deleting Pkd1 or Pkd2 in endothelial cells. At the cellular level, we have shown that Pkd deficient endothelial cells exhibit aberrant branching morphogenesis and altered directional migration. The specific signaling pathways regulated by polycystins in endothelial cells, however, are unknown. To understand the functional consequences of polycystin deficiency in endothelial cells we performed RNA sequencing (RNA-seq) in Pkd1-/- endothelial cells at two embryonic time points.


We harvested Pkd1-/- and littermate control embryos at E13.5 and E14.5 (N=36 total) and isolated endothelial cells using anti-CD31+ (specific marker for endothelial cells) coated magnetic beads. RNA was extracted and sequenced independently using 50bp single-end reads. Data was processed using Cutadapt and gene expression quantified using Salmon and R. Differential gene expression analysis was performed using DESeq2 package and enriched pathways were identified using clusterProfiler package.


We identified more than 200 genes that were differentially expressed (Log2 (FC)≤ ± 0.25 and a corrected p-value of <0.05) at each time point. At E13.5 functional clustering revealed an enrichment of genes expressing extracellular matrix components and genes involved in the innate immune response among top ranked. At E14.5, we found upregulation of genes related to cell migration, cell proliferation and angiogenesis probably as a mechanism to compensate the aberrantly developed embryonic vasculature. We found that the ATPase, H+ transporting, lysosomal V0 subunit C (Atp6v0c, Gene ID11984) was the most highly downregulated gene at both developmental stages analyzed, (Log2 FC= -1.61 and -1.50 respectively, and q= 0.00E+00 for both). Silencing of this gene was shown to effectively suppress migration and invasion of prostate cancer cells (PC-3M-1E8), which is relevant in the context of the migration defects we observe in Pkd mutant endothelial cells.


Our study revealed extensive transcriptional changes in Pkd1 mutant endothelial cells supporting the importance of polycystin signaling in endothelial cells and in vascular morphogenesis.


  • NIDDK Support