The FGF, TGFβ and WNT axis Modulate Self-renewal of Human SIX2+ Urine Derived Renal Progenitor Cells

Sci Rep. 2020 Jan 20;10(1):739. doi: 10.1038/s41598-020-57723-2.

Abstract

Human urine is a non-invasive source of renal stem cells with regeneration potential. Urine-derived renal progenitor cells were isolated from 10 individuals of both genders and distinct ages. These renal progenitors express pluripotency-associated proteins- TRA-1-60, TRA-1-81, SSEA4, C-KIT and CD133, as well as the renal stem cell markers -SIX2, CITED1, WT1, CD24 and CD106. The transcriptomes of all SIX2+ renal progenitors clustered together, and distinct from the human kidney biopsy-derived epithelial proximal cells (hREPCs). Stimulation of the urine-derived renal progenitor cells (UdRPCs) with the GSK3β-inhibitor (CHIR99021) induced differentiation. Transcriptome and KEGG pathway analysis revealed upregulation of WNT-associated genes- AXIN2, JUN and NKD1. Protein interaction network identified JUN- a downstream target of the WNT pathway in association with STAT3, ATF2 and MAPK1 as a putative negative regulator of self-renewal. Furthermore, like pluripotent stem cells, self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3 pathway. The urine-derived renal progenitor cells and the data presented should lay the foundation for studying nephrogenesis in human.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics
  • Cell Self Renewal / genetics*
  • Cell Self Renewal / physiology*
  • Female
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / physiology*
  • Gene Expression
  • Humans
  • Kidney / cytology*
  • Male
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / physiology*
  • Signal Transduction / genetics*
  • Signal Transduction / physiology*
  • Transcriptome
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*
  • Urine / cytology*
  • Wnt Signaling Pathway / genetics*
  • Wnt Signaling Pathway / physiology*

Substances

  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2