Open AccessCripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency
Author(s) -
Alessandro Fiorenzano,
Emilia Pascale,
Cristina D’Aniello,
Dario Acampora,
Cécilia Bassalert,
Francesco Russo,
Gennaro Andolfi,
Mauro Biffoni,
Federica Francescangeli,
Ann Zeuner,
Claudia Angelini,
Claire Chazaud,
Eduardo J. Patriarca,
Annalisa Fico,
Gabriella Minchiotti
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms12589
Subject(s) - epiblast , reprogramming , biology , induced pluripotent stem cell , embryonic stem cell , stem cell , microbiology and biotechnology , transdifferentiation , wnt signaling pathway , nodal signaling , cellular differentiation , genetics , gastrulation , cell , signal transduction , gene
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/β-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.