Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells.

Autor:	McCreery KP; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany., Stubb A; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki Finland., Stephens R; Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Fursova NA; System Biology of Gene Expression, National Cancer Institute, National Institute of Health, Bethesda, MD 20892., Cook A; Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Kruse K; Bioinformatics Service Unit, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany., Michelbach A; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany., Biggs LC; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki Finland., Keikhosravi A; High-Throughput Imaging Facility, National Cancer Institute, National Institute of Health, Bethesda, MD 20892., Nykänen S; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki Finland.; Gynecology and Obstetrics, Clinicum, University of Helsinki, 00290 Helsinki, Finland., Hydén-Granskog C; Helsinki University Hospital, Reproductive Medicine Unit, P.O. Box 150, 00029 HUS, Helsinki, Finland., Zou J; iPSC Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA., Lackmann JW; CECAD Research Center, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany., Niessen CM; Department Cell Biology of the Skin, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), Center for Molecular Medicine Cologne, University Hospital Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany., Vuoristo S; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki Finland.; Gynecology and Obstetrics, Clinicum, University of Helsinki, 00290 Helsinki, Finland.; Helsinki Institute of Life Science, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland., Miroshnikova YA; Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Wickström SA; Department of Cell and Tissue Dynamics, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.; Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki Finland.; Helsinki Institute of Life Science, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 07. Date of Electronic Publication: 2024 Sep 07.
DOI:	10.1101/2024.09.07.611779
Abstrakt:	Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although signaling circuits and gene regulatory networks that regulate pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations to control state transitions remains a fundamental open question. Here, we focus on two distinct models of pluripotency, primed pluripotent stem cells and pre-implantation inner cell mass cells of human embryos to discover that cell fate transitions associate with rapid changes in nuclear shape and volume which collectively alter the nuclear mechanophenotype. Mechanistic studies in human induced pluripotent stem cells further reveal that these phenotypical changes and the associated active fluctuations of the nuclear envelope arise from growth factor signaling-controlled changes in chromatin mechanics and cytoskeletal confinement. These collective mechano-osmotic changes trigger global transcriptional repression and a condensation-prone environment that primes chromatin for a cell fate transition by attenuating repression of differentiation genes. However, while this mechano-osmotic chromatin priming has the potential to accelerate fate transitions and differentiation, sustained biochemical signals are required for robust induction of specific lineages. Our findings uncover a critical mechanochemical feedback mechanism that integrates nuclear mechanics, shape and volume with biochemical signaling and chromatin state to control cell fate transition dynamics. Competing Interests: Declaration of interests The authors declare no conflict of interest.
Databáze:	MEDLINE
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