Mechanosensing of matrix by stem cells: From matrix heterogeneity, contractility, and the nucleus in pore-migration to cardiogenesis and muscle stem cells in vivo.
Mechanosensing of matrix by stem cells: From matrix heterogeneity, contractility, and the nucleus in pore-migration to cardiogenesis and muscle stem cells in vivo.
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DOI：
10.1016/j.semcdb.2017.05.025
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发表时间：
2017-11
影响因子：
7.3
通讯作者：
Discher DE
中科院分区：
文献类型：
--
作者：
Smith L;Cho S;Discher DE
干细胞是一种特殊的“可塑性”细胞类型，通过启动特定基因程序的表达，在各种信号的诱导下成为专门的、具有组织功能的谱系。基质硬度是多种干细胞类型可以感知和响应的信号之一。这篇论文式的综述主要集中在一些说明性干细胞类型的分化或早期成熟中基质弹性的机械传感，目标受众是生物学家和物理学家。由细胞的肌动蛋白-肌球蛋白细胞骨架施加的收缩力通常被细胞外基质抵抗，并通过粘附和细胞骨架最终转导到细胞核中以调节基因表达。复杂性增加了矩阵的异质性，并在一些模型系统中的明显的刚度异质性的仔细审查解决了一些争议矩阵mechanosensing。重要的是，局部刚度往往占主导地位，和'durotaxis'的干细胞向僵硬的矩阵揭示了依赖肌球蛋白-II力的产生和刚性微管，赋予方向性的持久迁移。3D中的干细胞和祖细胞迁移可进一步受到基质孔隙率以及刚度的影响，其中核大小和刚度影响生态位保留和命运选择。细胞通过刚性孔挤压甚至可以导致DNA损伤和基因组变化，这有助于向干细胞样状态去分化。肌动球蛋白的收缩是横纹肌的基本功能，横纹肌也表现出机械敏感性分化和成熟，如通过跳动的心脏细胞和骨骼肌干细胞的再生动员在体内所示。
Stem cells are particularly ‘plastic’ cell types that are induced by various cues to become specialized, tissuefunctional lineages by switching on the expression of specific gene programs. Matrix stiffness is among the cues that multiple stem cell types can sense and respond to. This seminar-style review focuses on mechanosensing of matrix elasticity in the differentiation or early maturation of a few illustrative stem cell types, with an intended audience of biologists and physical scientists. Contractile forces applied by a cell’s acto-myosin cytoskeleton are often resisted by the extracellular matrix and transduced through adhesions and the cytoskeleton ultimately into the nucleus to modulate gene expression. Complexity is added by matrix heterogeneity, and careful scrutiny of the evident stiffness heterogeneity in some model systems resolves some controversies concerning matrix mechanosensing. Importantly, local stiffness tends to dominate, and ‘durotaxis’ of stem cells toward stiff matrix reveals a dependence of persistent migration on myosin-II force generation and also rigid microtubules that confer directionality. Stem and progenitor cell migration in 3D can be further affected by matrix porosity as well as stiffness, with nuclear size and rigidity influencing niche retention and fate choices. Cell squeezing through rigid pores can even cause DNA damage and genomic changes that contribute to de-differentiation toward stem cell-like states. Contraction of acto-myosin is the essential function of striated muscle, which also exhibit mechanosensitive differentiation and maturation as illustrated in vivo by beating heart cells and by the regenerative mobilization of skeletal muscle stem cells.
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影响因子：
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