Plakoglobin is a mechanoresponsive regulator of naive pluripotency.

Autor: Kohler TN; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge, CB2 1QW, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK., De Jonghe J; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge, CB2 1QW, UK., Ellermann AL; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge, CB2 1QW, UK., Yanagida A; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.; Department of Veterinary Anatomy, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.; Stem Cell Therapy Laboratory, Advanced Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan., Herger M; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge, CB2 1QW, UK., Slatery EM; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK., Weberling A; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge, CB2 1QW, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK., Munger C; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge, CB2 1QW, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK., Fischer K; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge, CB2 1QW, UK., Mulas C; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.; Randall Centre for Cell and Molecular Biophysics, King's College London, London, SE1 1UL, UK.; Altos Labs, Cambridge Institute of Science, Cambridge, UK., Winkel A; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK., Ross C; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK.; MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK., Bergmann S; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK., Franze K; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK.; Institute of Medical Physics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Henkestr. 91, 91052, Erlangen, Germany.; Max-Planck-Zentrum für Physik und Medizin, 91054, Erlangen, Germany., Chalut K; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.; Altos Labs, Cambridge Institute of Science, Cambridge, UK., Nichols J; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK.; MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK., Boroviak TE; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK. teb45@cam.ac.uk.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, UK. teb45@cam.ac.uk.; Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK. teb45@cam.ac.uk., Hollfelder F; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge, CB2 1QW, UK. fh111@cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jul 07; Vol. 14 (1), pp. 4022. Date of Electronic Publication: 2023 Jul 07.
DOI: 10.1038/s41467-023-39515-0
Abstrakt: Biomechanical cues are instrumental in guiding embryonic development and cell differentiation. Understanding how these physical stimuli translate into transcriptional programs will provide insight into mechanisms underlying mammalian pre-implantation development. Here, we explore this type of regulation by exerting microenvironmental control over mouse embryonic stem cells. Microfluidic encapsulation of mouse embryonic stem cells in agarose microgels stabilizes the naive pluripotency network and specifically induces expression of Plakoglobin (Jup), a vertebrate homolog of β-catenin. Overexpression of Plakoglobin is sufficient to fully re-establish the naive pluripotency gene regulatory network under metastable pluripotency conditions, as confirmed by single-cell transcriptome profiling. Finally, we find that, in the epiblast, Plakoglobin was exclusively expressed at the blastocyst stage in human and mouse embryos - further strengthening the link between Plakoglobin and naive pluripotency in vivo. Our work reveals Plakoglobin as a mechanosensitive regulator of naive pluripotency and provides a paradigm to interrogate the effects of volumetric confinement on cell-fate transitions.
(© 2023. The Author(s).)
Databáze: MEDLINE
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