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Src family kinases and p38 mitogen-activated protein kinases regulate pluripotent cell differentiation in culture

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posted on 2023-05-18, 23:42 authored by Tan, BSN, Kwek, J, Wong, CKE, Saner, NJ, Yap, C, Felquer, F, Morris, MB, Gardner, DK, Rathjen, PD, Rathjen, J
Multiple pluripotent cell populations, which together comprise the pluripotent cell lineage, have been identified. The mechanisms that control the progression between these populations are still poorly understood. The formation of early primitive ectoderm-like (EPL) cells from mouse embryonic stem (mES) cells provides a model to understand how one such transition is regulated. EPL cells form from mES cells in response to l-proline uptake through the transporter Slc38a2. Using inhibitors of cell signaling we have shown that Src family kinases, p38 MAPK, ERK1/2 and GSK3β are required for the transition between mES and EPL cells. ERK1/2, c-Src and GSK3β are likely to be enforcing a receptive, primed state in mES cells, while Src family kinases and p38 MAPK are involved in the establishment of EPL cells. Inhibition of these pathways prevented the acquisition of most, but not all, features of EPL cells, suggesting that other pathways are required. L-proline activation of differentiation is mediated through metabolism and changes to intracellular metabolite levels, specifically reactive oxygen species. The implication of multiple signaling pathways in the process suggests a model in which the context of Src family kinase activation determines the outcomes of pluripotent cell differentiation.

History

Publication title

PLoS ONE

Volume

11

Issue

10

Article number

e0163244

Number

e0163244

Pagination

1-21

ISSN

1932-6203

Department/School

Menzies Institute for Medical Research

Publisher

Public Library of Science

Place of publication

United States

Rights statement

Copyright 2016 Tan et al. Licensed under Creative Commons 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Repository Status

  • Open

Socio-economic Objectives

Expanding knowledge in the biological sciences

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