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Plakoglobin is a mechanoresponsive regulator of naive pluripotency
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 regula...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329048/ https://www.ncbi.nlm.nih.gov/pubmed/37419903 http://dx.doi.org/10.1038/s41467-023-39515-0 |
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author | Kohler, Timo N. De Jonghe, Joachim Ellermann, Anna L. Yanagida, Ayaka Herger, Michael Slatery, Erin M. Weberling, Antonia Munger, Clara Fischer, Katrin Mulas, Carla Winkel, Alex Ross, Connor Bergmann, Sophie Franze, Kristian Chalut, Kevin Nichols, Jennifer Boroviak, Thorsten E. Hollfelder, Florian |
author_facet | Kohler, Timo N. De Jonghe, Joachim Ellermann, Anna L. Yanagida, Ayaka Herger, Michael Slatery, Erin M. Weberling, Antonia Munger, Clara Fischer, Katrin Mulas, Carla Winkel, Alex Ross, Connor Bergmann, Sophie Franze, Kristian Chalut, Kevin Nichols, Jennifer Boroviak, Thorsten E. Hollfelder, Florian |
author_sort | Kohler, Timo N. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10329048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103290482023-07-09 Plakoglobin is a mechanoresponsive regulator of naive pluripotency Kohler, Timo N. De Jonghe, Joachim Ellermann, Anna L. Yanagida, Ayaka Herger, Michael Slatery, Erin M. Weberling, Antonia Munger, Clara Fischer, Katrin Mulas, Carla Winkel, Alex Ross, Connor Bergmann, Sophie Franze, Kristian Chalut, Kevin Nichols, Jennifer Boroviak, Thorsten E. Hollfelder, Florian Nat Commun Article 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. Nature Publishing Group UK 2023-07-07 /pmc/articles/PMC10329048/ /pubmed/37419903 http://dx.doi.org/10.1038/s41467-023-39515-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Kohler, Timo N. De Jonghe, Joachim Ellermann, Anna L. Yanagida, Ayaka Herger, Michael Slatery, Erin M. Weberling, Antonia Munger, Clara Fischer, Katrin Mulas, Carla Winkel, Alex Ross, Connor Bergmann, Sophie Franze, Kristian Chalut, Kevin Nichols, Jennifer Boroviak, Thorsten E. Hollfelder, Florian Plakoglobin is a mechanoresponsive regulator of naive pluripotency |
title | Plakoglobin is a mechanoresponsive regulator of naive pluripotency |
title_full | Plakoglobin is a mechanoresponsive regulator of naive pluripotency |
title_fullStr | Plakoglobin is a mechanoresponsive regulator of naive pluripotency |
title_full_unstemmed | Plakoglobin is a mechanoresponsive regulator of naive pluripotency |
title_short | Plakoglobin is a mechanoresponsive regulator of naive pluripotency |
title_sort | plakoglobin is a mechanoresponsive regulator of naive pluripotency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329048/ https://www.ncbi.nlm.nih.gov/pubmed/37419903 http://dx.doi.org/10.1038/s41467-023-39515-0 |
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