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Publication : Epithelial cell plasticity drives endoderm formation during gastrulation.

First Author  Scheibner K Year  2021
Journal  Nat Cell Biol Volume  23
Issue  7 Pages  692-703
PubMed ID  34168324 Mgi Jnum  J:307834
Mgi Id  MGI:6725705 Doi  10.1038/s41556-021-00694-x
Citation  Scheibner K, et al. (2021) Epithelial cell plasticity drives endoderm formation during gastrulation. Nat Cell Biol 23(7):692-703
abstractText  It is generally accepted that epiblast cells ingress into the primitive streak by epithelial-to-mesenchymal transition (EMT) to give rise to the mesoderm; however, it is less clear how the endoderm acquires an epithelial fate. Here, we used embryonic stem cell and mouse embryo knock-in reporter systems to combine time-resolved lineage labelling with high-resolution single-cell transcriptomics. This allowed us to resolve the morphogenetic programs that segregate the mesoderm from the endoderm germ layer. Strikingly, while the mesoderm is formed by classical EMT, the endoderm is formed independent of the key EMT transcription factor Snail1 by mechanisms of epithelial cell plasticity. Importantly, forkhead box transcription factor A2 (Foxa2) acts as an epithelial gatekeeper and EMT suppressor to shield the endoderm from undergoing a mesenchymal transition. Altogether, these results not only establish the morphogenetic details of germ layer formation, but also have broader implications for stem cell differentiation and cancer metastasis.
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