Three-dimensional geometry controls division symmetry in stem cell colonies.
Three-dimensional geometry controls division symmetry in stem cell colonies.
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DOI：
10.1242/jcs.255018
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发表时间：
2021-07-15
影响因子：
4
通讯作者：
Paluch EK
中科院分区：
文献类型：
--
作者：
Chaigne A;Smith MB;Lopez Cavestany R;Hannezo E;Chalut KJ;Paluch EK
正确控制分裂方向和对称性，主要由纺锤体定位决定，对发育和体内平衡至关重要。纺锤体定位已在二维（2D）环境和上皮组织中分裂的细胞中被广泛研究，其中蛋白质如NuMA（也称为NUMA 1）使分裂沿着细胞的间期长轴定向。然而，很少有人知道细胞如何控制纺锤体定位在三维（3D）环境中，如早期哺乳动物胚胎和各种成人组织。在这里，我们使用小鼠胚胎干细胞（ESC），在3D集落中生长，作为研究3D分裂的模型。我们观察到，在3D集落的外围，ESC显示高纺锤体移动性和不对称分裂。我们的数据表明，增强纺锤体运动是由于不平等的分布之间的细胞连接蛋白E-钙粘蛋白未来的子细胞。有趣的是，当细胞向分化方向发展时，分裂变得更加对称，在中期具有更长的形状，并在后期增强皮质NuMA募集。总之，这项研究表明，在3D环境中，细胞的几何形状及其与邻居的接触控制分裂方向和对称性。总结：小鼠胚胎干细胞在3D集落中显示不对称分裂，细胞-细胞连接和细胞几何形状是分裂对称性的关键调节因子。
Proper control of division orientation and symmetry, largely determined by spindle positioning, is essential to development and homeostasis. Spindle positioning has been extensively studied in cells dividing in two-dimensional (2D) environments and in epithelial tissues, where proteins such as NuMA (also known as NUMA1) orient division along the interphase long axis of the cell. However, little is known about how cells control spindle positioning in three-dimensional (3D) environments, such as early mammalian embryos and a variety of adult tissues. Here, we use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate division in 3D. We observe that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell–cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry. Summary: Mouse embryonic stem cells display asymmetric divisions in 3D colonies, with cell–cell junctions and cell geometry acting as key regulators of division symmetry.