Identification of the central intermediate in the extra-embryonic to embryonic endoderm transition through single-cell transcriptomics
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Identification of the central intermediate in the extra-embryonic to embryonic endoderm transition through single-cell transcriptomics. / Rothová, Michaela Mrugala; Nielsen, Alexander Valentin; Proks, Martin; Wong, Yan Fung; Riveiro, Alba Redo; Linneberg-Agerholm, Madeleine; David, Eyal; Amit, Ido; Trusina, Ala; Brickman, Joshua Mark.
In: Nature Cell Biology, Vol. 24, No. 6, 2022, p. 833-844.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of the central intermediate in the extra-embryonic to embryonic endoderm transition through single-cell transcriptomics
AU - Rothová, Michaela Mrugala
AU - Nielsen, Alexander Valentin
AU - Proks, Martin
AU - Wong, Yan Fung
AU - Riveiro, Alba Redo
AU - Linneberg-Agerholm, Madeleine
AU - David, Eyal
AU - Amit, Ido
AU - Trusina, Ala
AU - Brickman, Joshua Mark
N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41556-022-00923-x
DO - 10.1038/s41556-022-00923-x
M3 - Journal article
C2 - 35681011
AN - SCOPUS:85131161702
VL - 24
SP - 833
EP - 844
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 6
ER -
ID: 311118955