Plakoglobin is a mechanoresponsive regulator of naive pluripotency
| Autor: | 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 |
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| Přispěvatelé: | Kohler, Timo N [0000-0003-1949-0655], Ellermann, Anna L [0000-0002-3713-2870], Slatery, Erin M [0000-0002-9097-6618], Weberling, Antonia [0000-0001-8282-5695], Munger, Clara [0000-0003-0672-1602], Fischer, Katrin [0000-0002-6566-3038], Chalut, Kevin [0000-0001-6200-9690], Boroviak, Thorsten E [0000-0001-8703-8949], Hollfelder, Florian [0000-0002-1367-6312], Apollo - University of Cambridge Repository |
| Rok vydání: | 2023 |
| Předmět: |
Mammals
1.1 Normal biological development and functioning Gene Expression Profiling Stem Cell Research - Embryonic - Non-Human Embryonic Development Cell Differentiation 3101 Biochemistry and Cell Biology Stem Cell Research Mice Blastocyst Genetics 1 Underpinning research Animals Humans Stem Cell Research - Nonembryonic - Non-Human Generic health relevance gamma Catenin Germ Layers 31 Biological Sciences |
| DOI: | 10.17863/cam.96441 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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