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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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 FOXA2Venus 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 naïve 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.

TidsskriftNature Cell Biology
Udgave nummer6
Sider (fra-til)833-844
Antal sider12
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Work in our groups was supported by grants from the Lundbeck Foundation (R198-2015-412), J.M.B.; Independent Research Fund Denmark (8020-00100B and 6110-00009), J.M.B.; the Novo Nordisk Foundation (NNF17OC0028218), J.M.B.; the Danish National Research Foundation (DNRF116), J.M.B. and A.T. The Novo Nordisk Foundation Center for Stem Cell Medicine is supported by Novo Nordisk Foundation (NNF21CC0073729), and its predecessor The Novo Nordisk Foundation Center for Stem Cell Biology was also supported by the Novo Nordisk Foundation (NNF17CC0027852).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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