Mechanisms Regulating Muscle Stem Cell Homeostasis

骨骼肌组织在哺乳动物生物体的一生中得到修复和维持，但也可以被修复和维持。 受疾病和老年人的影响。成体干细胞负责再生和主要- 骨骼肌组织是罕见的卫星细胞，占总肌核的2-4%。卫星 细胞因其在骨骼肌组织中的解剖学定位而命名，在骨骼肌组织中这些细胞通常是静止的 并且位于肌纤维的质膜和基底膜之间。当在- 静止的卫星细胞通过顺序地“激活”，进入细胞周期，增殖， 然后进行终末分化和融合以修复受损的肌纤维或融合 形成新的肌纤维少数卫星细胞自我更新，重新获得静止的细胞。 状态和重新占用卫星小区生态位，以提供持续的维护和修理。的严重程度 肌肉损伤会招募卫星细胞，这些细胞会扩张以修复损伤，然后恢复到损伤前的数量 一旦再生完成。什么信号负责终止卫星细胞扩张期间 再生？卫星细胞何时在体内自我更新？肌肉损伤的“严重程度”如何招募sat- 精英细胞？一旦再生，什么机制确保卫星细胞以损伤前的数量重新建立- 行动完成了吗？我们已经确定了卫星细胞和入侵细胞之间的细胞间相互作用， 在肌肉损伤后4天至7天之间，似乎调节卫星细胞数量。数字- 入侵细胞的数量与肌肉损伤的严重程度直接相关，因此可能会调节卫星细胞， 与受伤严重程度相称的数字。我们认为细胞对肌肉损伤的非自主反应 将肌肉损伤的程度直接传递给扩张的卫星细胞，使干细胞能够适应 并确保适当数量的祖细胞可用于修复和自我再生， newal来重新填充干细胞库。如果得到证实，骨骼肌的细胞非自主调节 干细胞库代表了将组织损伤程度传递给常驻干细胞的新范例， 将确定新的治疗靶点，以操纵卫星细胞的数量，并可能改善细胞移植， 以及肌肉再生。

Skeletal muscle tissue is repaired and maintained for the lifetime of mammalian organisms but can be compromised by diseases and in aged individuals. The adult stem cell responsible for regenerating and main- taining skeletal muscle tissue is the rare satellite cell, comprising 2-4% of the total muscle nuclei. The satellite cell is named for its anatomical localization in skeletal muscle tissue, where these cells are typically quiescent and lie sandwiched between the plasma membrane of the myofiber and the basement membrane. When in- jured, the quiescent satellite cell responds by sequentially “activating,” entering the cell cycle, proliferating as progenitors and then undergoing terminal differentiation and fusion to repair damaged myofibers or fusion with each other to form new myofibers. A small number of satellite cells self-renew, re-acquiring a quiescent state and re-occupying the satellite cell niche to provide continuous maintenance and repair. The severity of a muscle injury recruits satellite cells, which expand to repair the damage and then, return to pre-injury numbers once regeneration is completed. What signals are responsible for terminating satellite cell expansion during regeneration? When do satellite cells self-renew in vivo? How does the “severity” of a muscle injury recruit sat- ellite cells? What mechanisms ensure that satellite cells are re-established at pre-injury numbers once regener- ation is complete? We have identified a cell-cell interaction between satellite cells and invading cells appearing between 4 days and 7 days following a muscle injury that appears to regulate satellite cell numbers. The num- bers of invading cells directly correlate with the severity of a muscle injury and thus, may regulate satellite cell numbers commensurate with injury severity. We posit that a cell non-autonomous response to a muscle injury conveys the extent of muscle damage directly to the expanding satellite cells, enabling the stem cells to appro- priately respond and ensuring the appropriate numbers of progenitors are available for repair and for self-re- newal to repopulate the stem cell pool. If confirmed, the cell non-autonomous regulation of the skeletal muscle stem cell pool represents a new paradigm for conveying the extent of tissue damage to a resident stem cell and will identify new therapeutic targets to manipulate satellite cell number and potentially improve cell transplan- tation as well as muscle regeneration.