Single‐molecule tracking of Nanog and Oct4 in living mouse embryonic stem cells uncovers a feedback mechanism of pluripotency maintenance
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- Kazuko Okamoto
- Laboratory for Comprehensive Bioimaging RIKEN Center for Biosystems Dynamics Research (BDR) Kobe Japan
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- Hideaki Fujita
- Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine Hiroshima University Higashi‐Hiroshima Japan
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- Yasushi Okada
- Laboratory for Cell Polarity Regulation RIKEN Center for Biosystems Dynamics Research (BDR) Osaka Japan
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- Soya Shinkai
- Laboratory for Developmental Dynamics RIKEN Center for Biosystems Dynamics Research (BDR) Kobe Japan
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- Shuichi Onami
- Laboratory for Developmental Dynamics RIKEN Center for Biosystems Dynamics Research (BDR) Kobe Japan
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- Kuniya Abe
- Technology and Development Team for Mammalian Genome Dynamics RIKEN BioResource Research Center (BRC) Tsukuba Japan
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- Kenta Fujimoto
- Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine Hiroshima University Higashi‐Hiroshima Japan
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- Kensuke Sasaki
- Laboratory for Comprehensive Bioimaging RIKEN Center for Biosystems Dynamics Research (BDR) Kobe Japan
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- Go Shioi
- Laboratory for Comprehensive Bioimaging RIKEN Center for Biosystems Dynamics Research (BDR) Kobe Japan
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- Tomonobu M Watanabe
- Laboratory for Comprehensive Bioimaging RIKEN Center for Biosystems Dynamics Research (BDR) Kobe Japan
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説明
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
収録刊行物
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- The EMBO Journal
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The EMBO Journal 42 (18), 2023-08-23
Springer Science and Business Media LLC