Mechanochemical control of epidermal stem cell divisions by B-plexins.
Mechanochemical control of epidermal stem cell divisions by B-plexins.
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DOI：
10.1038/s41467-021-21513-9
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发表时间：
2021-02-26
影响因子：
16.6
通讯作者：
Worzfeld T
中科院分区：
文献类型：
--
作者：
Jiang C;Javed A;Kaiser L;Nava MM;Xu R;Brandt DT;Zhao D;Mayer B;Fernández-Baldovinos J;Zhou L;Höß C;Sawmynaden K;Oleksy A;Matthews D;Weinstein LS;Hahn H;Gröne HJ;Graumann PL;Niessen CM;Offermanns S;Wickström SA;Worzfeld T
对细胞增殖的精确时空控制是上皮组织形态发生的关键。上皮细胞分裂导致组织拥挤和局部力量分布的变化，进而抑制细胞分裂的速度。然而，这种机械反馈背后的分子机制在很大程度上还不清楚。在这里，我们确定了在胚胎皮肤发育过程中，B-丛蛋白跨膜受体在应对拥挤诱导的机械力方面的关键需求。缺乏B-丛的表皮干细胞无法感知机械压迫，导致转录辅助激活因子YAP的抑制、过度增殖和组织过度生长。从力学上讲，我们发现B-神经丛通过稳定黏附细胞连接和降低皮质硬度来调节对拥挤的机械反应。最后，我们提供的证据表明，依赖于B-丛蛋白的机械力化学反馈也与限制最常见皮肤癌类型--基底细胞癌的肿瘤生长的病理生理学相关。我们的数据定义了B-丛蛋白在机械感觉中的核心作用，将细胞密度和细胞分裂结合在发育和疾病中。目前尚不清楚上皮组织如何根据细胞密度调整细胞分裂率。在这里，作者表明，丛状蛋白-B1和丛状蛋白-B2感觉到表皮干细胞的机械压缩(拥挤)，导致YAP失活和细胞增殖受到抑制。
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.
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影响因子：
4
作者：
Chugh P;Paluch EK
通讯作者：
Paluch EK
影响因子：
5.3
作者：
Deng, Suhua;Hirschberg, Alexandra;Kuner, Rohini
通讯作者：
Kuner, Rohini
DOI：
10.1007/978-1-4939-6448-2_1
发表时间：
2017
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Alto LT;Terman JR
通讯作者：
Terman JR
影响因子：
21.3
作者：
Engl, W.;Arasi, B.;Viasnoff, V.
通讯作者：
Viasnoff, V.
影响因子：
8
作者：
Argast, G. M.;Croy, C. H.;Ahn, N. G.
通讯作者：
Ahn, N. G.