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Publication : Identification of the central intermediate in the extra-embryonic to embryonic endoderm transition through single-cell transcriptomics.

First Author  Rothová MM Year  2022
Journal  Nat Cell Biol Volume  24
Issue  6 Pages  833-844
PubMed ID  35681011 Mgi Jnum  J:332314
Mgi Id  MGI:7414428 Doi  10.1038/s41556-022-00923-x
Citation  Rothova MM, et al. (2022) Identification of the central intermediate in the extra-embryonic to embryonic endoderm transition through single-cell transcriptomics. Nat Cell Biol 24(6):833-844
abstractText  High-resolution maps of embryonic development suggest that acquisition of cell identity is not limited to canonical germ layers but proceeds via alternative routes. Despite evidence that visceral organs are formed via embryonic and extra-embryonic trajectories, the production of organ-specific cell types in vitro focuses on the embryonic one. Here we resolve these differentiation routes using massively parallel single-cell RNA sequencing to generate datasets from FOXA2(Venus) reporter mouse embryos and embryonic stem cell differentiation towards endoderm. To relate cell types in these datasets, we develop a single-parameter computational approach and identify an intermediate en route from extra-embryonic identity to embryonic endoderm, which we localize spatially in embryos at embryonic day 7.5. While there is little evidence for this cell type in embryonic stem cell differentiation, by following the extra-embryonic trajectory starting with naive extra-embryonic endoderm stem cells we can generate embryonic gut spheroids. Exploiting developmental plasticity therefore offers alternatives to pluripotent cells and opens alternative avenues for in vitro differentiation.
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