Concise Review: Regulation of Embryonic Stem Cell Lineage Commitment by Mitogen‐Activated Protein Kinases

Embryonic stem (ES) cells can give rise, in vivo, to the ectodermal, endodermal, and mesodermal germ layers and, in vitro, can differentiate into multiple cell lineages, offering broad perspectives in regenerative medicine. Understanding the molecular mechanisms governing ES cell commitment is an es...

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Published in:Stem cells (Dayton, Ohio) Vol. 25; no. 5; pp. 1090 - 1095
Main Authors: Binétruy, Bernard, Heasley, Lynn, Bost, Frédéric, Caron, Leslie, Aouadi, Myriam
Format: Journal Article
Language:English
Published: Bristol John Wiley & Sons, Ltd 01-05-2007
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Summary:Embryonic stem (ES) cells can give rise, in vivo, to the ectodermal, endodermal, and mesodermal germ layers and, in vitro, can differentiate into multiple cell lineages, offering broad perspectives in regenerative medicine. Understanding the molecular mechanisms governing ES cell commitment is an essential challenge in this field. The mitogen‐activated protein kinase (MAPK) pathways extracellular signal‐regulated kinase (ERK), c‐Jun amino‐terminal kinase (JNK), and p38MAPK are able to regulate ES commitment from early steps of the process to mature differentiated cells. Whereas the ERK pathway inhibits the self‐renewal of ES cells, upon commitment this pathway is involved in the development of extraembryonic tissues, in early mesoderm differentiation, and in the formation of mature adipocytes; p38MAPK displays a large spectrum of action from neurons to adipocytes, and JNK is involved in both ectoderm and primitive endoderm differentiations. Furthermore, for a given pathway, several of these effects are isoform‐dependent, revealing the complexity of the cellular response to activation of MAPK pathways. Regarding tissue regeneration, the potential outcome of systematic analysis of the function of different MAPKs in different ES cell differentiation programs is discussed. Disclosure of potential conflicts of interest is found at the end of this article.
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ISSN:1066-5099
1549-4918
DOI:10.1634/stemcells.2006-0612