ERK signalling eliminates Nanog and maintains Oct4 to drive the formative pluripotency transition.

Autor:	Mulas C; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.; Randall Centre for Cell and Molecular Biology, King's College London, London SE1 1YR, UK.; Altos Labs Cambridge Institute of Science, Granta Park, Cambridge CB21 6GP, UK., Stammers M; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK., Salomaa SI; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.; Altos Labs Cambridge Institute of Science, Granta Park, Cambridge CB21 6GP, UK., Heinzen C; Institute of Cell Biology and Neuroscience, Goethe University, Frankfurt 60439, Germany., Suter DM; Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland., Smith A; Living Systems Institute, University of Exeter, Exeter EX4 4QD, UK., Chalut KJ; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.; Altos Labs Cambridge Institute of Science, Granta Park, Cambridge CB21 6GP, UK.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2024 Jul 15; Vol. 151 (14). Date of Electronic Publication: 2024 Jul 26.
DOI:	10.1242/dev.203106
Abstrakt:	Naïve epiblast cells in the embryo and pluripotent stem cells in vitro undergo developmental progression to a formative state competent for lineage specification. During this transition, transcription factors and chromatin are rewired to encode new functional features. Here, we examine the role of mitogen-activated protein kinase (ERK1/2) signalling in pluripotent state transition. We show that a primary consequence of ERK activation in mouse embryonic stem cells is elimination of Nanog, which precipitates breakdown of the naïve state gene regulatory network. Variability in pERK dynamics results in heterogeneous loss of Nanog and metachronous state transition. Knockdown of Nanog allows exit without ERK activation. However, transition to formative pluripotency does not proceed and cells collapse to an indeterminate identity. This outcome is due to failure to maintain expression of the central pluripotency factor Oct4. Thus, during formative transition ERK signalling both dismantles the naïve state and preserves pluripotency. These results illustrate how a single signalling pathway can both initiate and secure transition between cell states. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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