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Retinoic acid signaling is critical during the totipotency window in early mammalian development.

Nat. Struct. Mol. Biol. 28, 521-532 (2021)
Publ. Version/Full Text DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Totipotent cells hold enormous potential for regenerative medicine. Thus, the development of cellular models recapitulating totipotent-like features is of paramount importance. Cells resembling the totipotent cells of early embryos arise spontaneously in mouse embryonic stem (ES) cell cultures. Such ‘2-cell-like-cells’ (2CLCs) recapitulate 2-cell-stage features and display expanded cell potential. Here, we used 2CLCs to perform a small-molecule screen to identify new pathways regulating the 2-cell-stage program. We identified retinoids as robust inducers of 2CLCs and the retinoic acid (RA)-signaling pathway as a key component of the regulatory circuitry of totipotent cells in embryos. Using single-cell RNA-seq, we reveal the transcriptional dynamics of 2CLC reprogramming and show that ES cells undergo distinct cellular trajectories in response to RA. Importantly, endogenous RA activity in early embryos is essential for zygotic genome activation and developmental progression. Overall, our data shed light on the gene regulatory networks controlling cellular plasticity and the totipotency program.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Embryonic Stem-cells; Receptors Rars; Diffusion Maps; Mouse; Differentiation; Transcription; Activation; Expression; Chromatin; Gene
ISSN (print) / ISBN 1545-9993
e-ISSN 1545-9985
Quellenangaben Volume: 28, Issue: 6, Pages: 521-532 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Grants EMBO fellowship
H2020 Marie-Curie Action ChromDesign
H2020 Marie-Curie Action ITN EpiSystem
German Research Council
HMGU Small Molecule projects (Developmental projects)
Helmholtz Association