Mechanisms Regulating Muscle Stem Cell Homeostasis

骨骼肌组织在哺乳动物的一生中得到修复和维持，但可以 因疾病和老年个体而受到损害。成体干细胞负责再生和主要- 骨骼肌组织是一种罕见的卫星细胞，占肌细胞核总数的2-4%。这颗卫星 细胞因其在骨骼肌组织中的解剖定位而得名，在骨骼肌组织中，这些细胞通常是静止的 夹在肌纤维质膜和基底膜之间。在以下情况下- 静止的卫星细胞通过顺序地“激活”，进入细胞周期，增殖为 然后进行末端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，重新获得静止状态 状态和重新占用卫星单元壁龛，以提供持续的维护和维修。一场灾难的严重性 肌肉损伤招募卫星细胞，卫星细胞扩张以修复损伤，然后恢复到受伤前的数量 一旦再生完成。什么信号负责终止卫星细胞的扩展 再生？卫星细胞在体内什么时候自我更新？一名肌肉受伤新兵的“严重性”如何- 卫星电池？是什么机制确保卫星细胞一旦恢复，就能以受伤前的数量重建- 交易完成了吗？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 在肌肉损伤后的4天到7天之间，似乎调节卫星细胞的数量。数字-- 侵袭细胞的BERS与肌肉损伤的严重程度直接相关，因此可能调节卫星细胞 与受伤严重程度相称的人数。我们假设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正在扩张的卫星细胞，使干细胞能够接近于 适当地回应，并确保有适当数量的祖细胞可供修复和自我修复 重新填充干细胞库的新方法。如果得到证实，该细胞对骨骼肌的非自主调节 干细胞库代表了一种新的范例，可以将组织损伤的程度传递给常驻干细胞 将确定新的治疗靶点来操纵卫星细胞数量并潜在地改善细胞移植计划- 转体和肌肉再生。

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.