Mechanochemical control of epidermal stem cell divisions by B-plexins
| Autor: | Jiang, Chen, Javed, Ahsan, Kaiser, Laura, Nava, Michele M., Xu, Rui, Brandt, Dominique T., Zhao, Dandan, Mayer, Benjamin, Fernández-Baldovinos, Javier, Zhou, Luping, Höß, Carsten, Sawmynaden, Kovilen, Oleksy, Arkadiusz, Matthews, David, Weinstein, Lee S., Hahn, Heidi, Gröne, Hermann-Josef, Graumann, Peter L., Niessen, Carien M., Offermanns, Stefan, Wickström, Sara A., Worzfeld, Thomas |
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| Přispěvatelé: | Helsinki Institute of Life Science HiLIFE, University of Helsinki, Department of Biochemistry and Developmental Biology, STEMM - Stem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Keratinocytes
Plexins animal structures Stem cell mechanics Science Organogenesis Mitosis Embryonic Development Nerve Tissue Proteins Receptors Cell Surface Article Epithelium Mice Cell Adhesion Morphogenesis Animals Cell proliferation Stem Cells 1184 Genetics developmental biology physiology Epithelial Cells Intercellular Junctions Epidermal Cells Carcinoma Basal Cell embryonic structures Basal cell carcinoma 1182 Biochemistry cell and molecular biology Female Epidermis Carrier Proteins Cell Adhesion Molecules Cell Division Skin stem cells |
| Zdroj: | Nature Communications Nat Commun Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) |
| ISSN: | 2041-1723 |
| Popis: | The precise spatiotemporal control of cell proliferation is key to the morphogenesis of epithelial tissues. Epithelial cell divisions lead to tissue crowding and local changes in force distribution, which in turn suppress the rate of cell divisions. However, the molecular mechanisms underlying this mechanical feedback are largely unclear. Here, we identify a critical requirement of B-plexin transmembrane receptors in the response to crowding-induced mechanical forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail to sense mechanical compression, resulting in disinhibition of the transcriptional coactivator YAP, hyperproliferation, and tissue overgrowth. Mechanistically, we show that B-plexins mediate mechanoresponses to crowding through stabilization of adhesive cell junctions and lowering of cortical stiffness. Finally, we provide evidence that the B-plexin-dependent mechanochemical feedback is also pathophysiologically relevant to limit tumor growth in basal cell carcinoma, the most common type of skin cancer. Our data define a central role of B-plexins in mechanosensation to couple cell density and cell division in development and disease. It is unclear how epithelial tissues adjust cell division rates to cell density. Here, the authors show that Plexin-B1 and Plexin-B2 sense mechanical compression (crowding) of epidermal stem cells, resulting in inactivation of YAP and suppression of cell proliferation. |
| Databáze: | OpenAIRE |
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