Myc depletion induces a pluripotent dormant state mimicking diapause

Please always quote using this URN: urn:nbn:de:bvb:20-opus-190868
  • Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause.Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.show moreshow less

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Author: Roberta Scognamiglio, Nina Cabezas-Wallscheid, Marc Christian Thier, Sandro Altamura, Alejandro Reyes, Áine M. Prendergast, Daniel Baumgärtner, Larissa S. Carnevalli, Ann Atzberger, Simon Haas, Lisa von Paleske, Thorsten Boroviak, Philipp Wörsdörfer, Marieke A. G. Essers, Ulrich Kloz, Robert N. Eisenman, Frank Edenhofer, Paul Bertone, Wolfgang Huber, Franciscus van der Hoeven, Austin Smith, Andreas Trumpp
URN:urn:nbn:de:bvb:20-opus-190868
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Language:English
Parent Title (English):Cell
Year of Completion:2016
Volume:164
Issue:4
Pagenumber:668-680
Source:Cell (2016) 164:4, S. 668-680. https://doi.org/10.1016/j.cell.2015.12.033
DOI:https://doi.org/10.1016/j.cell.2015.12.033
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:N-Myc; c-Myc; embryonic stem cells; gene expression; hematopoietic stem cells; leukemia inhibitory factor; protein synthesis; self-renewal
Release Date:2021/02/02
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International