Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal
Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal
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DOI：
10.1016/j.ydbio.2004.08.015
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发表时间：
2004-11-15
影响因子：
2.7
通讯作者：
Olwin, BB
中科院分区：
文献类型：
--
作者：
Olguin, HC;Olwin, BB
卫星细胞是骨骼肌再生的前体细胞。卫星细胞在Pax-7（-/-）小鼠中不存在，表明该转录因子对于卫星细胞特化是至关重要的[西尔，P.，萨布林，洛杉矶，Girgis-Gabardo，A.，Mandarin，A.，Gruss，P.，Rudnicki，硕士，2000. Pax 7是肌源性卫星细胞的特化所必需的。Cell 102，777-786]。Pax-7在活化卫星细胞中的表达分析意外地揭示了个体克隆内的实质性异质性。进一步的分析表明，Pax-7和肌细胞生成素的表达在分化过程中是相互排斥的，其中Pax-7似乎在逃避分化和退出细胞周期的细胞中上调，这表明这两种转录因子之间的调节关系。事实上，Pax-7的过表达下调MyoD，阻止肌细胞生成素诱导，并阻断MyoD诱导的10 T1/2细胞的肌细胞转化。Pax-7的过表达甚至在增殖条件下也促进细胞周期退出。总之，这些结果表明，Pax-7可能在允许激活的卫星细胞重新获得静止的未分化状态方面发挥关键作用。这些数据支持的概念，卫星细胞自我更新可能是补充的卫星细胞隔室在骨骼肌再生的主要机制。(C)2004年爱思唯尔公司All rights reserved.
Satellite cells are myogenic precursors responsible for skeletal muscle regeneration. Satellite cells are absent in the Pax-7(-/-) mouse, suggesting that this transcription factor is crucial for satellite cell specification [Seale, P., Sabourin, L.A., Girgis-Gabardo, A., Mansouri, A., Gruss, P., Rudnicki, M.A., 2000. Pax7 is required for the specification of myogenic satellite cells. Cell 102, 777-786]. Analysis of Pax-7 expression in activated satellite cells unexpectedly revealed substantial heterogeneity within individual clones. Further analyses show that Pax-7 and myogenin expression are mutually exclusive during differentiation, where Pax-7 appears to be up-regulated in cells that escape differentiation and exit the cell cycle, suggesting a regulatory relationship between these two transcription factors. Indeed, overexpression of Pax-7 down-regulates MyoD, prevents myogenin induction, and blocks MyoD-induced myogenic conversion of 10T1/2 cells. Overexpression of Pax-7 also promotes cell cycle exit even in proliferation conditions. Together, these results suggest that Pax-7 may play a crucial role in allowing activated satellite cells to reacquire a quiescent, undifferentiated state. These data support the concept that satellite cell self-renewal may be a primary mechanism for replenishment of the satellite cell compartment during skeletal muscle regeneration. (C) 2004 Elsevier Inc. All rights reserved.