p38 mitogen activated protein kinase controls two successive-steps during the early mesodermal commitment of embryonic stem cells.: P38 CONTROLS THE MESODERMAL COMMITMENT OF ES CELLS

Abstract : Embryonic stem (ES) cells differentiate in vitro into all cell lineages. We previously found that the p38 mitogen activated kinase (p38MAPK) pathway controls the commitment of ES cells toward either cardiomyogenesis (p38 on) or neurogenesis (p38 off ). In this study, we show that p38α knock-out ES cells do not differentiate into cardiac, endothelial, smooth muscle, and skeletal muscle lineages. Reexpression of p38MAPK in these cells partially rescues their mesodermal differentiation defects and corrects the high level of spontaneous neurogenesis of knock-out cells. Wild-type ES cells were treated with a p38MAPK-specific inhibitor during the differentiation process. These experiments allowed us to identify 2 early independent successive p38MAPK functions in the formation of mesodermal lineages. Further, the first one correlates with the regulation of the expression of Brachyury, an essential mesodermal-specific transcription factor, by p38MAPK. In conclusion, by genetic and biochemical approaches, we demonstrate that p38MAPK activity is essential for the commitment of ES cell into cardiac, endothelial, smooth muscle, and skeletal muscle mesodermal lineages.
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Stem Cells and Development, Mary Ann Liebert, 2011, 20 (7), pp.1233-46. 〈10.1089/scd.2010.0213〉
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Soumis le : vendredi 4 novembre 2011 - 07:00:06
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Emilie Barruet, Ola Hadadeh, Franck Peiretti, Valérie Renault, Yasmine Hadjal, et al.. p38 mitogen activated protein kinase controls two successive-steps during the early mesodermal commitment of embryonic stem cells.: P38 CONTROLS THE MESODERMAL COMMITMENT OF ES CELLS. Stem Cells and Development, Mary Ann Liebert, 2011, 20 (7), pp.1233-46. 〈10.1089/scd.2010.0213〉. 〈inserm-00532566〉

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