The PI3K pathway balances self-renewal and differentiation of nephron progenitor cells through β-catenin signaling

Stem Cell Reports. 2015 Apr 14;4(4):551-60. doi: 10.1016/j.stemcr.2015.01.021. Epub 2015 Mar 5.

Abstract

Nephron progenitor cells differentiate to form nephrons during embryonic kidney development. In contrast, self-renewal maintains progenitor numbers and premature depletion leads to impaired kidney function. Here we analyze the PI3K pathway as a point of convergence for the multiple pathways that are known to control self-renewal in the kidney. We demonstrate that a reduction in PI3K signaling triggers premature differentiation of the progenitors and activates a differentiation program that precedes the mesenchymal-to-epithelial transition through ectopic activation of the β-catenin pathway. Therefore, the combined output of PI3K and other pathways fine-tunes the balance between self-renewal and differentiation in nephron progenitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Self Renewal*
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Nephrons / cytology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Stem Cells / cytology*
  • Stem Cells / metabolism*
  • beta Catenin / metabolism*

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • beta Catenin
  • Proto-Oncogene Proteins c-akt