Single-molecule tracking of Nanog and Oct4 in living mouse embryonic stem cells uncovers a feedback mechanism of pluripotency maintenance.

Autor: Okamoto K; Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.; Amphibian Research Center, Hiroshima University, Hiroshima, Japan., Fujita H; Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Higashi-Hiroshima, Japan., Okada Y; Laboratory for Cell Polarity Regulation, RIKEN Center for Biosystems Dynamics Research (BDR), Osaka, Japan.; Department of Cell Biology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Physics, Universal Biology Institute (UBI), Graduate School of Science, The University of Tokyo, Tokyo, Japan.; International Research Center for Neurointelligence (WPI-IRCN), Institutes for Advanced Study, The University of Tokyo, Tokyo, Japan., Shinkai S; Laboratory for Developmental Dynamics, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.; Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), Hiroshima University, Hiroshima, Japan., Onami S; Laboratory for Developmental Dynamics, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan., Abe K; Technology and Development Team for Mammalian Genome Dynamics, RIKEN BioResource Research Center (BRC), Tsukuba, Japan., Fujimoto K; Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Higashi-Hiroshima, Japan., Sasaki K; Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan., Shioi G; Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan., Watanabe TM; Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.; Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Higashi-Hiroshima, Japan.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Sep 18; Vol. 42 (18), pp. e112305. Date of Electronic Publication: 2023 Aug 23.
DOI: 10.15252/embj.2022112305
Abstrakt: Nanog and Oct4 are core transcription factors that form part of a gene regulatory network to regulate hundreds of target genes for pluripotency maintenance in mouse embryonic stem cells (ESCs). To understand their function in the pluripotency maintenance, we visualised and quantified the dynamics of single molecules of Nanog and Oct4 in a mouse ESCs during pluripotency loss. Interestingly, Nanog interacted longer with its target loci upon reduced expression or at the onset of differentiation, suggesting a feedback mechanism to maintain the pluripotent state. The expression level and interaction time of Nanog and Oct4 correlate with their fluctuation and interaction frequency, respectively, which in turn depend on the ESC differentiation status. The DNA viscoelasticity near the Oct4 target locus remained flexible during differentiation, supporting its role either in chromatin opening or a preferred binding to uncondensed chromatin regions. Based on these results, we propose a new negative feedback mechanism for pluripotency maintenance via the DNA condensation state-dependent interplay of Nanog and Oct4.
(© 2023 The Authors.)
Databáze: MEDLINE
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