Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Bioessays. 2023 May;45(5):e2200249. doi: 10.1002/bies.202200249. Epub 2023 Mar 14.
Cellular mechanisms whereby quiescent stem cells sense tissue injury and transition to an activated state are largely unknown. Quiescent skeletal muscle stem cells (MuSCs, also called satellite cells) have elaborate, heterogeneous projections that rapidly retract in response to muscle injury. They may therefore act as direct sensors of their niche environment. Retraction is driven by a Rac-to-Rho GTPase activity switch that promotes downstream MuSC activation events. These and other observations lead to several hypotheses: (1) projections are morphologically dynamic at quiescence, providing a surveillance function for muscle damage; (2) quiescent projection dynamics are regulated by the relative balance of Rac and Rho activities promoted by niche-derived cues; (3) projections, particularly their associated filopodia, sense tissue damage via changes to the biomechanical properties of the niche and/or detection of signaling cues released by damaged myofibers; and (4) the dynamic nature of projections results in a population of MuSCs with heterogeneous functional properties. These concepts may extend to other types of quiescent stem cells, as well as prove useful in translational research settings.
静止状态的干细胞如何感知组织损伤并转变为激活状态，其细胞机制在很大程度上尚不清楚。静止状态的骨骼肌干细胞（也称为卫星细胞）具有精细且异质的突起，这些突起会在肌肉损伤时迅速缩回。因此，它们可能充当其生态位环境的直接传感器。回缩是由 Rac 到 Rho GTPase 活性开关驱动的，该开关促进了下游的 MuSC 激活事件。这些和其他观察结果提出了几个假设：（1）突起在静止时具有形态动力学，为肌肉损伤提供了监视功能；（2）静止突起动力学受来自生态位的线索促进的 Rac 和 Rho 活性的相对平衡调节；（3）突起，特别是其相关的丝状伪足，通过改变生态位的生物力学特性和/或检测受损肌纤维释放的信号转导线索来感知组织损伤；（4）突起的动态性质导致 MuSC 群体具有异质的功能特性。这些概念可能适用于其他类型的静止干细胞，并在转化研究环境中证明有用。
