Plakoglobin is a mechanoresponsive regulator of naive pluripotency

Kohler TN, De Jonghe J, Ellermann AL, Yanagida A, Herger M, Slatery EM, Weberling A, Munger C, Fischer K, Mulas C, Winkel A, Ross C, Bergmann S, Franze K, Chalut K, Nichols J, Boroviak TE, Hollfelder F (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 14

Article Number: 4022

Journal Issue: 1

DOI: 10.1038/s41467-023-39515-0

Abstract

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.

Authors with CRIS profile

Kristian Franze Lehrstuhl für Medizinische Physik und Mikrogewebetechnik

Involved external institutions

University of Cambridge GB United Kingdom (GB)

How to cite

APA:

Kohler, T.N., De Jonghe, J., Ellermann, A.L., Yanagida, A., Herger, M., Slatery, E.M.,... Hollfelder, F. (2023). Plakoglobin is a mechanoresponsive regulator of naive pluripotency. Nature Communications, 14(1). https://dx.doi.org/10.1038/s41467-023-39515-0

MLA:

Kohler, Timo N., et al. "Plakoglobin is a mechanoresponsive regulator of naive pluripotency." Nature Communications 14.1 (2023).

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