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

Stem Cell Reports
Nils Olof LindströmPeter Hohenstein

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.

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Citations

Feb 10, 2016·Differentiation; Research in Biological Diversity·Shunsuke Tanigawa, Alan O Perantoni
Mar 5, 2016·Developmental Biology·Manish KumarPradeep S Tanwar
Sep 8, 2015·Stem Cell Reports·Guillermo López-RuanoÁngel Hernández-Hernández
Jul 11, 2016·European Journal of Pharmacology·Aleksandra Rak-Raszewska, Seppo Vainio
Aug 24, 2016·FEBS Letters·Paramjeet SinghMohd Jamal Dar
Aug 21, 2018·Annual Review of Cell and Developmental Biology·Leif Oxburgh
Jul 30, 2017·Journal of the American Society of Nephrology : JASN·Jiao LiuZubaida Saifudeen
Dec 5, 2015·Nature Communications·Sree Deepthi MuthukrishnanLeif Oxburgh
Nov 30, 2018·Frontiers in Physiology·Kristen KurtzebornSatu Kuure
Apr 9, 2020·Frontiers in Cell and Developmental Biology·Niloofar Khoshdel RadReza Moghadasali
Feb 17, 2018·Journal of the American Society of Nephrology : JASN·Nils O LindströmAndrew P McMahon
Feb 17, 2018·Journal of the American Society of Nephrology : JASN·Nils O LindströmAndrew P McMahon
Oct 23, 2020·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Giovane G TorteloteZubaida Saifudeen
Nov 19, 2021·Journal of the American Society of Nephrology : JASN·Melissa H Little, Benjamin D Humphreys

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Methods Mentioned

BETA
gene knockouts
Assay

Software Mentioned

Ensemble

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