Mesenchymal stem cells (MSCs) from adult tissues are promising candidates for personalized cell therapy and tissue engineering. Significant progress was achieved in our understanding of the regulation of MSCs proliferation and differentiation by different cues during the past years. Proliferation and differentiation of MSCs are sensitive to the extracellular matrix (ECM) properties, physical cues, and chemical signaling. Sheath stress, matrix stiffness, surface adhesiveness, and micro- and nanotopography define cell shape and dictate lineage commitment of MSCs even in the absence of specific chemical signals. We discuss mechanotransduction as the major route from ECM through the cytoskeleton toward signaling pathways and gene expression. All components of the cytoskeleton from primary cilium and focal adhesions (FAs) to actin, microtubules (MTs), and intermediate filaments (IFs) are involved in the mechanotransduction. Differentiation of MSCs is regulated via the complex network of interrelated signaling pathways, including RhoA/ROCK, Akt/Erk, and YAP/TAZ effectors of Hippo pathway. These pathways could be regulated both by chemical and mechanical stimuli. Attenuation of these pathways in MSCs results in specific changes in FAs and actin cytoskeleton. Besides, differentiation of MSCs affects MTs and IFs. Recent findings highlight the role of intranuclear actin in the regulation of transcription factors in response to mechanical environmental stimuli. Alterations of cytoskeletal components reflect the MSC senescence state and their migratory capacity. In this review, we discuss the relationships between the molecular interactions in signaling pathways and morphological response of cytoskeletal components and reveal the complex interrelations between cytoskeleton systems and signaling pathways during lineage commitment of MSCs. Impact Statement This review describes the complex network of relationships between mechanical and biochemical stimuli in mesenchymal stem cells (MSC) and their balance which defines the morphological changes of cell shape due to rearrangement of cytoskeletal systems during lineage commitment of MSCs.

中文翻译：

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间充质干细胞中的谱系承诺，信号传导途径和细胞骨架系统。

来自成人组织的间充质干细胞（MSC）是个性化细胞疗法和组织工程的有希望的候选者。在过去几年中，我们对MSCs增殖和分化的不同线索的了解取得了重要进展。MSC的增殖和分化对细胞外基质（ECM）特性，物理线索和化学信号敏感。鞘应力，基质刚度，表面粘附性以及微观和纳米形貌定义了细胞形状，并决定了MSC的谱系承诺，即使在没有特定化学信号的情况下也是如此。我们讨论机械转导是从ECM通过细胞骨架向信号通路和基因表达的主要途径。从初次纤毛和粘着斑（FAs）到肌动蛋白，微管（MTs），机械转导涉及中间丝（IF）。MSC的分化是通过相互关联的信号通路的复杂网络调节的，这些信号通路包括Hippo通路的RhoA / ROCK，Akt / Erk和YAP / TAZ效应子。这些途径可以通过化学和机械刺激来调节。MSC中这些途径的减弱导致FA和肌动蛋白细胞骨架的特定变化。此外，MSC的分化会影响MT和IF。最近的发现突出了核内肌动蛋白在响应机械环境刺激而调节转录因子中的作用。细胞骨架成分的改变反映了MSC的衰老状态及其迁移能力。在这篇评论中 我们讨论了信号通路中的分子相互作用与细胞骨架成分的形态学反应之间的关系，并揭示了MSCs沿袭期间细胞骨架系统与信号通路之间的复杂相互关系。影响陈述本综述描述了间充质干细胞（MSC）的机械和生化刺激之间的复杂关系网络及其平衡，该平衡定义了由于MSCs沿袭过程中细胞骨架系统重排导致的细胞形状形态变化。