Ependymal cells (ECs) are multiciliated cells in the brain that contribute to cerebrospinal fluid flow. ECs are specified during embryonic stages but differentiate later in development. Their differentiation depends on genes such as GEMC1 and MCIDAS in conjunction with E2F4/5 as well as on cell-cycle-related factors. In the mouse brain, we observe that nuclear deformation accompanies EC differentiation. Tampering with these deformations either by decreasing F-actin levels or by severing the link between the nucleus and the actin cytoskeleton blocks differentiation. Conversely, increasing F-actin by knocking out the Arp2/3 complex inhibitor Arpin or artificially deforming the nucleus activates differentiation. These data are consistent with actin polymerization triggering nuclear deformation and jump starting the signaling that produces ECs. A player in this process is the retinoblastoma 1 (RB1) protein, whose phosphorylation prompts MCIDAS activation. Overall, this study identifies a role for actin-based mechanical inputs to the nucleus as controlling factors in cell differentiation.

中文翻译：

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基于肌动蛋白的细胞核变形控制小鼠多纤毛室管膜细胞分化


室管膜细胞 （EC） 是大脑中的多纤毛细胞，有助于脑脊液流动。ECs 在胚胎阶段被指定，但在发育后期分化。它们的分化取决于 GEMC1 和 MCIDAS 等基因以及 E2F4/5 以及细胞周期相关因素。在小鼠大脑中，我们观察到核变形伴随着 EC 分化。通过降低 F-肌动蛋白水平或通过切断细胞核和肌动蛋白细胞骨架之间的联系来破坏这些变形，从而阻断分化。相反，通过敲除 Arp2/3 复合物抑制剂 Arpin 或人为使细胞核变形来增加 F-肌动蛋白会激活分化。这些数据与肌动蛋白聚合触发核变形并快速启动产生 ECs 的信号传导一致。在此过程中，视网膜母细胞瘤 1 （RB1） 蛋白发挥了作用，其磷酸化会促进 MCIDAS 激活。总体而言，本研究确定了基于肌动蛋白的细胞核机械输入作为细胞分化的控制因素的作用。