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Open Access Green as soon as Postprint is submitted to ZB.
Combinatorial microRNA activity is essential for the transition of pluripotent cells from proliferation into dormancy.
Genome Res. 34, 572-589 (2024)
Dormancy is a key feature of stem cell function in adult tissues as well as in embryonic cells in the context of diapause. The establishment of dormancy is an active process that involves extensive transcriptional, epigenetic, and metabolic rewiring. How these processes are coordinated to successfully transition cells to the resting dormant state remains unclear. Here we show that microRNA activity, which is otherwise dispensable for preimplantation development, is essential for the adaptation of early mouse embryos to the dormant state of diapause. In particular, the pluripotent epiblast depends on miRNA activity, the absence of which results in the loss of pluripotent cells. Through the integration of high-sensitivity small RNA expression profiling of individual embryos and protein expression of miRNA targets with public data of protein-protein interactions, we constructed the miRNA-mediated regulatory network of mouse early embryos specific to diapause. We find that individual miRNAs contribute to the combinatorial regulation by the network, and the perturbation of the network compromises embryo survival in diapause. We further identified the nutrient-sensitive transcription factor TFE3 as an upstream regulator of diapause-specific miRNAs, linking cytoplasmic MTOR activity to nuclear miRNA biogenesis. Our results place miRNAs as a critical regulatory layer for the molecular rewiring of early embryos to establish dormancy.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Embryonic Stem-cells; Dicer; Implantation; Blastocysts; Progression; Biogenesis; Induction; Recovery; Dgcr8; Genes
ISSN (print) / ISBN
1088-9051
e-ISSN
1549-5469
Journal
Genome Research
Quellenangaben
Volume: 34,
Issue: 4,
Pages: 572-589
Publisher
Cold Spring Harbor Laboratory Press
Publishing Place
1 Bungtown Rd, Cold Spring Harbor, Ny 11724 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
Grants
Sofja Kovalevskaja Award (Humboldt Foundation)
Max Planck Society
Deutsche Forschungsgemeinschaft
German Academic Exchange Service (DAAD)
Max Planck Society
Deutsche Forschungsgemeinschaft
German Academic Exchange Service (DAAD)