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Publication : Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency.

First Author  Fiorenzano A Year  2016
Journal  Nat Commun Volume  7
Pages  12589 PubMed ID  27586544
Mgi Jnum  J:242105 Mgi Id  MGI:5904418
Doi  10.1038/ncomms12589 Citation  Fiorenzano A, et al. (2016) Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency. Nat Commun 7:12589
abstractText  Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/beta-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo.
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