Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells.
Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells.
复制标题
间充质干细胞中 N-钙粘蛋白连接可逆转 YAP 的力学驱动核定位
DOI：
10.1038/s41467-021-26454-x
复制
发表时间：
2021-10-28
影响因子：
16.6
通讯作者：
Lin M
中科院分区：
文献类型：
--
作者：
Zhang C;Zhu H;Ren X;Gao B;Cheng B;Liu S;Sha B;Li Z;Zhang Z;Lv Y;Wang H;Guo H;Lu TJ;Xu F;Genin GM;Lin M
间充质干细胞的分化途径是基于机械感知的累积效应。细胞的机械微环境在发育过程中发生了很大的变化，从细胞通常被其他细胞包围的早期开始，一直持续到细胞通常被细胞外基质包围的后期。细胞是如何清除这些机械微环境中的一些记忆，同时锁定其他记忆的，目前尚不清楚。在这里，我们开发了一种材料和培养系统，用于修改和测量细胞保留机械感应累积效应的程度。使用该系统，我们发现纤维连接蛋白的RGD粘附基序（细胞外基质的代表）的作用，已知通过核YAP定位在间充质干细胞中赋予通常称为“机械记忆”的作用，被n -钙粘蛋白的HAVDI粘附基序（细胞-细胞接触的代表）所消除。这些影响可以通过一个电机离合器模型来解释，该模型与细胞牵引力、核变形和由此产生的核YAP重新定位有关。结果表明，通过定义和可编程的材料系统，可以控制间充质干细胞中与机械记忆相关的蛋白质的储存和去除。间充质干细胞的分化途径是基于其生长环境中的机械因素，并在整个发育过程中发生变化。在这里，作者开发了一种材料和培养系统来修改和测量细胞保留机械感应累积效应的程度，以探索细胞如何在锁定其他记忆的同时消除某些线索的记忆。
Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell’s mechanical microenvironment changes substantially over the course of development, beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed “mechanical memory” in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems. Mesenchymal stem cells adopt differentiation pathways based upon mechanical cues in their environment which change throughout development. Here the authors develop a material and culture system to modify and measure the degree to which cells retain cumulative effects of mechanosensing to explore how cells erase the memory of some cues while locking in memory of others.
登录
查看更多内容
机械敏感的miRNA偏置通过MTOR信号传导人类间充质干细胞命运。
影响因子：
16.6
作者：
Frith JE;Kusuma GD;Carthew J;Li F;Cloonan N;Gomez GA;Cooper-White JJ
通讯作者：
Cooper-White JJ
影响因子：
21.3
作者：
Case LB;Waterman CM
通讯作者：
Waterman CM
影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
粘着斑蛋白在三维细胞运动中的独特作用。
影响因子：
21.3
作者：
Fraley, Stephanie I.;Feng, Yunfeng;Krishnamurthy, Ranjini;Kim, Dong-Hwee;Celedon, Alfredo;Longmore, Gregory D.;Wirtz, Denis
通讯作者：
Wirtz, Denis
影响因子：
21.3
作者：
Bertocchi C;Wang Y;Ravasio A;Hara Y;Wu Y;Sailov T;Baird MA;Davidson MW;Zaidel-Bar R;Toyama Y;Ladoux B;Mege RM;Kanchanawong P
通讯作者：
Kanchanawong P