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Hammoud, A.A.* ; Kirstein, N.* ; Mournetas, V.* ; Darracq, A.* ; Broc, S.* ; Blanchard, C.* ; Zeineddine, D.* ; Mortada, M.* ; Boeuf, H.*

Murine embryonic stem cell plasticity is regulated through klf5 and maintained by metalloproteinase mmp1 and hypoxia.

PLoS ONE 11:e0146281 (2016)
DOI
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Mouse embryonic stem cells (mESCs) are expanded and maintained pluripotent in vitro in the presence of leukemia inhibitory factor (LIF), an IL6 cytokine family member which displays pleiotropic functions, depending on both cell maturity and cell type. LIF withdrawal leads to heterogeneous differentiation of mESCs with a proportion of the differentiated cells apoptosising. During LIF withdrawal, cells sequentially enter a reversible and irreversible phase of differentiation during which LIF addition induces different effects. However the regulators and effectors of LIF-mediated reprogramming are poorly understood. By employing a LIF-dependent 'plasticity' test, that we set up, we show that Klf5, but not JunB is a key LIF effector. Furthermore PI3K signaling, required for the maintenance of mESC pluripotency, has no effect on mESC plasticity while displaying a major role in committed cells by stimulating expression of the mesodermal marker Brachyury at the expense of endoderm and neuroectoderm lineage markers. We also show that the MMP1 metalloproteinase, which can replace LIF for maintenance of pluripotency, mimics LIF in the plasticity window, but less efficiently. Finally, we demonstrate that mESCs maintain plasticity and pluripotency potentials in vitro under hypoxic/physioxic growth conditions at 3% O2 despite lower levels of Pluri and Master gene expression in comparison to 20% O2.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: e0146281 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)