Inhibition of JAK-STAT signaling stimulates adult satellite cell function.
Inhibition of JAK-STAT signaling stimulates adult satellite cell function.
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骨骼肌的再生能力减弱发生在成年期。我们确定了减少小鼠成体卫星细胞的内在能力，以促进再生和重新填充的小生境。基因表达分析鉴定了3周龄和18月龄小鼠之间JAK/STAT信号传导靶标的表达增加。敲除Jak 2或Stat 3显著刺激培养肌纤维上的对称卫星干细胞分裂。敲除Jak 2或Stat 3在前瞻性分离的卫星细胞显着增强了他们的能力，重新填充卫星细胞龛。药理学抑制Jak 2和Stat 3类似地刺激卫星细胞在体外的对称扩增和它们在体内的植入。肌肉注射这些药物导致肌肉修复和力量产生的显着增强。总之，这些结果揭示了功能上区分成体卫星细胞的内在特性，并提出了治疗肌肉萎缩性疾病的有前途的治疗途径。
Diminished regenerative capacity of skeletal muscle occurs during adulthood. We identified a reduction in the intrinsic capacity of murine adult satellite cells to contribute to regeneration and repopulate the niche. Gene expression analysis identified an increase in expression of JAK/STAT signaling targets between 3 week old and 18 month old mice. Knockdown of Jak2 or Stat3 significantly stimulated symmetric satellite stem cell divisions on cultured myofibers. Knockdown of Jak2 or Stat3 in prospectively isolated satellite cells markedly enhanced their ability to repopulate the satellite cell niche. Pharmacological inhibition of Jak2 and Stat3 similarly stimulated symmetric expansion of satellite cells in vitro and their engraftment in vivo. Intramuscular injection of these drugs resulted in a dramatic enhancement of muscle repair and force generation. Together these results reveal intrinsic properties that functionally distinguish adult satellite cells and suggest a promising therapeutic avenue for the treatment of muscle wasting diseases.
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影响因子：
5.5
作者：
McKay, Bryon R.;Ogborn, Daniel I.;Parise, Gianni
通讯作者：
Parise, Gianni
影响因子：
11.8
作者：
Conboy, IM;Rando, TA
通讯作者：
Rando, TA
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
影响因子：
23.9
作者：
Bentzinger, C. Florian;Wang, Yu Xin;von Maltzahn, Julia;Soleimani, Vahab D.;Yin, Hang;Rudnicki, Michael A.;Rudnicki, A.
通讯作者：
Rudnicki, A.
影响因子：
82.9
作者：
通讯作者：
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