A Strong Contractile Actin Fence and Large Adhesions Direct Human Pluripotent Colony Morphology and Adhesion.
A Strong Contractile Actin Fence and Large Adhesions Direct Human Pluripotent Colony Morphology and Adhesion.
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DOI：
10.1016/j.stemcr.2017.05.021
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发表时间：
2017-07-11
影响因子：
5.9
通讯作者：
Ivaska J
中科院分区：
文献类型：
--
作者：
Närvä E;Stubb A;Guzmán C;Blomqvist M;Balboa D;Lerche M;Saari M;Otonkoski T;Ivaska J
细胞类型特异性的功能和身份受到细胞骨架和细胞外基质（ECM）之间相互作用的严格调节。人多能干细胞（hPSC）具有最终的分化能力和异常低强度的ECM接触，然而粘附位点和相关肌动蛋白细胞骨架的组织和功能仍然不清楚。我们用全内反射荧光显微镜对细胞-ECM界面处的hPSC进行成像，发现在殖民地边缘的粘附异常大，并由厚的腹侧应力纤维连接。发现包围殖民地的肌动蛋白栅栏施加广泛的Rho-ROCK-肌球蛋白依赖性机械应力，以加强菌落形态、压实和多能性，并确定有丝分裂纺锤体方向。值得注意的是，分化改变了粘附组织和信号传导，其特征在于从腹侧到背侧应力纤维的切换，降低机械应力，并增加整合素活性和细胞-ECM粘附强度。因此，多能性似乎与独特的集落组织和粘附结构有关。人类多能集落具有特殊的肌动蛋白结构和粘着斑收缩依赖的紧密集落压实增强多能性集落形态通过边缘定向的细胞分裂维持分化改变肌动蛋白方向、整合素活性和粘附强度Ivaska和同事证明人类多能集落被大的粘着斑包围，粘着斑由厚的肌动蛋白腹侧应力纤维连接。他们表明，所产生的Rho信号传导依赖性肌动蛋白栅栏强制多能性，并决定集落形态，压实，有丝分裂纺锤体的方向，并粘附到ECM。
Cell-type-specific functions and identity are tightly regulated by interactions between the cell cytoskeleton and the extracellular matrix (ECM). Human pluripotent stem cells (hPSCs) have ultimate differentiation capacity and exceptionally low-strength ECM contact, yet the organization and function of adhesion sites and associated actin cytoskeleton remain poorly defined. We imaged hPSCs at the cell-ECM interface with total internal reflection fluorescence microscopy and discovered that adhesions at the colony edge were exceptionally large and connected by thick ventral stress fibers. The actin fence encircling the colony was found to exert extensive Rho-ROCK-myosin-dependent mechanical stress to enforce colony morphology, compaction, and pluripotency and to define mitotic spindle orientation. Remarkably, differentiation altered adhesion organization and signaling characterized by a switch from ventral to dorsal stress fibers, reduced mechanical stress, and increased integrin activity and cell-ECM adhesion strength. Thus, pluripotency appears to be linked to unique colony organization and adhesion structure. Human pluripotent colonies have exceptional actin structure and focal adhesions Contraction-dependent tight colony compaction enforces pluripotency Colony morphology is maintained by edge-oriented cell divisions Differentiation alters actin orientation, integrin activity, and adhesion strength Ivaska and colleagues demonstrate that human pluripotent colonies are encircled by large focal adhesions that are connected by thick actin ventral stress fibers. They show that resulting Rho-signaling dependent actin fence enforces pluripotency and dictates colony morphology, compaction, mitotic spindle orientation, and adhesion to ECM.
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影响因子：
3.7
作者：
Chowdhury F;Li Y;Poh YC;Yokohama-Tamaki T;Wang N;Tanaka TS
通讯作者：
Tanaka TS
DOI：
10.1073/pnas.1106377109
发表时间：
2012-01-31
影响因子：
11.1
作者：
Tseng, Qingzong;Duchemin-Pelletier, Eve;Thery, Manuel
通讯作者：
Thery, Manuel
影响因子：
9.2
作者：
Timpson, P;Jones, GE;Brunton, VG
通讯作者：
Brunton, VG
系统地识别人IPSC产生的障碍。
影响因子：
64.5
作者：
Qin H;Diaz A;Blouin L;Lebbink RJ;Patena W;Tanbun P;LeProust EM;McManus MT;Song JS;Ramalho-Santos M
通讯作者：
Ramalho-Santos M
影响因子：
16.6
作者：
Robertson, Joseph;Jacquemet, Guillaume;Byron, Adam;Jones, Matthew C.;Warwood, Stacey;Selley, Julian N.;Knight, David;Humphries, Jonathan D.;Humphries, Martin J.
通讯作者：
Humphries, Martin J.