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Abstract: TH-PO739

Selected Renal Cells Express a Podocyte-Parietal Epithelial Cell Transcriptome

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Narayan, Prakash, ProKidney, Winston-Salem, North Carolina, United States
  • Bruce, Andrew T., ProKidney, Winston-Salem, North Carolina, United States
  • Bertram, Tim A., ProKidney, Winston-Salem, North Carolina, United States
  • Jain, Deepak, ProKidney, Winston-Salem, North Carolina, United States
Background

Selected renal cells (SRCs) express podocyte, ureteric bud and cap mesenchyme markers and in models of chronic kidney disease (CKD) their administration is associated with improved glomerular barrier function, renal filtration, and preservation of renal microarchitecture and glomerular integrity. We tested the hypothesis that SRCs share a podocyte-parietal epithelial cell (PEC) transcriptome associated with renal repair and restoration.

Methods

The intersection set of podocyte-PEC genes (literature) and directionally aligned SRC genes were seeded into miRNet and Cytoscape for visualization of the shared transcriptome and identification of its functional attributes. Human SRCs (National Disease Research Interchange kidneys) were submitted to scRNA-seq to map gene expression and placed in culture and the supernatant queried for secreted vascular endothelial growth factor A (VEGFA) and its angiogenic activity using a human umbilical vein endothelial cell (HUVEC) tube formation assay.

Results

osr1, six2, lhx1, fgf8, lfng, nphs1, nphs2, vegfa, cd44 and hes1 are expressed by both podocyte-PEC and SRCs and involved in kidney developmental functions including maintenance of undifferentiated nephron precursors, tube and nephron formation, maturation of the glomerular barrier and formation of the glomerular capillary bed (A, B). Vegfa emerged as the hub gene within this network (C). SRCs expressed vegfa (D) and secreted VEGFA (0.75 to 3.02 ng/mL, mean=1.45 ng/mL) whose angiogenic activity was evidenced by HUVEC tube formation (E).

Conclusion

A Vegfa anchored podocyte-PEC transcriptome expressed by SRCs may recapitulate events associated with kidney development and mediate the preservation or improvement of glomerular integrity, renal microarchitecture and renal filtration observed in CKD models.

(A, B) SRCs express podocyte-PEC genes involved in kidney development including glomerular development. (C) The shared podocyte-PEC and SRC transcriptome. (D) Vegfa is expressed by SRCs whose secreted gene product is associated with tube formation in HUVECs (E, arrows).

Funding

  • Commercial Support – ProKidney