Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency.
Alessandro FiorenzanoEmilia PascaleCristina D'AnielloDario AcamporaCecilia BassalertFrancesco RussoGennaro AndolfiMauro BiffoniFederica FrancescangeliAnn ZeunerClaudia AngeliniClaire ChazaudEduardo J PatriarcaAnnalisa FicoGabriella MinchiottiPublished in: Nature communications (2016)
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.
Keyphrases
- stem cells
- cell fate
- single cell
- endothelial cells
- cell therapy
- transcription factor
- epithelial mesenchymal transition
- induced pluripotent stem cells
- embryonic stem cells
- cell proliferation
- squamous cell carcinoma
- hiv infected
- transforming growth factor
- lymph node
- mesenchymal stem cells
- pregnant women
- replacement therapy
- rectal cancer