The PI3K pathway balances self-renewal and differentiation of Nephron Progenitor Cells through β-catenin signaling

Nils Olof Lindström; Neil Oliver Carragher; Peter Hohenstein

doi:10.1016/j.stemcr.2015.01.021

The PI3K pathway balances self-renewal and differentiation of Nephron Progenitor Cells through β-catenin signaling

Nils Olof Lindström^*, Neil Oliver Carragher, Peter Hohenstein

^*Corresponding author for this work

Medicine, Nephrology Division

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 b-catenin pathway. Therefore, the combined output of PI3K and other pathways fine-tunes the balance between self-renewal and differentiation in nephron progenitors.

Original language	English (US)
Pages (from-to)	551-560
Number of pages	10
Journal	Stem cell reports
Volume	4
Issue number	4
DOIs	https://doi.org/10.1016/j.stemcr.2015.01.021
State	Published - 2015

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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@article{66e9671cb4944ff698b3d85083c9c239,

title = "The PI3K pathway balances self-renewal and differentiation of Nephron Progenitor Cells through β-catenin signaling",

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 b-catenin pathway. Therefore, the combined output of PI3K and other pathways fine-tunes the balance between self-renewal and differentiation in nephron progenitors.",

author = "Lindstr{\"o}m, {Nils Olof} and Carragher, {Neil Oliver} and Peter Hohenstein",

note = "Funding Information: We thank the members of the Hohenstein lab for valuable discussions. We thank Shahida Sheraz and Anna Thornburn for help with animals, and Bob Fleming, Matt Pearson, Paul Perry, and Ann Wheeler for advice on microscopy and fluorescence-activated cell sorting (FACS). N.O.L was supported by the National Centre for Replacement, Refinement and Reduction of Animals in Research (Grant 94808). The Roslin Institute receives Institute Strategic Programme Grant funding from the Biotechnology and Biological Sciences Research Council (BB/J004316/1). ",

year = "2015",

doi = "10.1016/j.stemcr.2015.01.021",

language = "English (US)",

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pages = "551--560",

journal = "Stem Cell Reports",

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T1 - The PI3K pathway balances self-renewal and differentiation of Nephron Progenitor Cells through β-catenin signaling

AU - Lindström, Nils Olof

AU - Carragher, Neil Oliver

AU - Hohenstein, Peter

N1 - Funding Information: We thank the members of the Hohenstein lab for valuable discussions. We thank Shahida Sheraz and Anna Thornburn for help with animals, and Bob Fleming, Matt Pearson, Paul Perry, and Ann Wheeler for advice on microscopy and fluorescence-activated cell sorting (FACS). N.O.L was supported by the National Centre for Replacement, Refinement and Reduction of Animals in Research (Grant 94808). The Roslin Institute receives Institute Strategic Programme Grant funding from the Biotechnology and Biological Sciences Research Council (BB/J004316/1).

PY - 2015

Y1 - 2015

N2 - 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 b-catenin pathway. Therefore, the combined output of PI3K and other pathways fine-tunes the balance between self-renewal and differentiation in nephron progenitors.

AB - 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 b-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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