During the last decades intermediate filaments (IFs) have emerged as important regulators of cellular signaling events, ascribing IFs with functions beyond the structural support they provide. The organ and developmental stage‐specific expression of IFs regulate cell differentiation within developing or remodeling tissues. Lack of IFs causes perturbed stem cell differentiation in vasculature, intestine, nervous system, and mammary gland, in transgenic mouse models. The aberrant cell fate decisions are caused by deregulation of different stem cell signaling pathways, such as Notch, Wnt, YAP/TAZ, and TGFβ. Mutations in genes coding for IFs cause an array of different diseases, many related to stem cell dysfunction, but the molecular mechanisms remain unresolved. Here, we provide a comprehensive overview of how IFs interact with and regulate the activity, localization and function of different signaling proteins in stem cells, and how the assembly state and PTM profile of IFs may affect these processes. Identifying when, where and how IFs and cell signaling congregate, will expand our understanding of IF‐linked stem cell dysfunction during development and disease.

中文翻译：

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从结构弹性到细胞规格——中间丝作为细胞命运的调节剂

在过去的几十年中，中间丝 (IF) 已成为细胞信号事件的重要调节器，将 IF 的功能归因于它们提供的结构支持之外。IFs 的器官和发育阶段特异性表达调节发育或重塑组织内的细胞分化。在转基因小鼠模型中，缺乏 IF 会导致脉管系统、肠道、神经系统和乳腺中的干细胞分化受到干扰。异常的细胞命运决定是由不同干细胞信号通路的失调引起的，例如 Notch、Wnt、YAP/TAZ 和 TGFβ。编码 IF 的基因突变会导致一系列不同的疾病，其中许多与干细胞功能障碍有关，但分子机制仍未得到解决。这里，我们全面概述了 IF 如何与干细胞中不同信号蛋白的活性、定位和功能相互作用并对其进行调节，以及 IF 的组装状态和 PTM 谱如何影响这些过程。确定 IF 和细胞信号传导的时间、地点和方式，将扩大我们对发育和疾病过程中 IF 相关干细胞功能障碍的理解。