Myf5-positive satellite cells contribute to Pax7-dependent long-term maintenance of adult muscle stem cells.

Myf5-positive satellite cells contribute to Pax7-dependent long-term maintenance of adult muscle stem cells.
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DOI:
10.1016/j.stem.2013.07.016
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发表时间:
2013-11-07
期刊:
影响因子:
23.9
通讯作者:
Braun, Thomas
Braun, Thomas
中科院分区:
医学1区
文献类型:
--
作者:
Guenther, Stefan;Kim, Johnny;Kostin, Sawa;Lepper, Christoph;Fan, Chen-Ming;Braun, Thomas

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骨骼肌含有表达Pax7的肌肉干细胞或卫星细胞,使肌肉在成年后的大部分时间内再生。在这里,我们证明,诱导失活Pax7表达细胞的成年小鼠导致肌肉干细胞的损失和减少异染色质凝聚在罕见的幸存卫星细胞。Myf5表达细胞中Pax7的失活揭示了大多数成体肌肉干细胞来源于肌源性谱系,其表达肌源性调节因子Myf5或MyoD。同样,大多数肌肉干细胞在成年期从表达Myf5的肌源性细胞中补充,肌肉损伤后表达Myf5的细胞中Pax7的失活导致肌肉再生的完全停滞。最后,我们证明了相对少量的肌肉干细胞足以有效修复骨骼肌。我们的结论是,Pax7的行为在不同的水平在一个非分级的监管网络控制肌肉卫星细胞介导的肌肉再生。
Skeletal muscle contains Pax7-expressing muscle stem or satellite cells, enabling muscle regeneration throughout most of adult life. Here, we demonstrate that induced inactivation of Pax7 in Pax7-expressing cells of adult mice leads to loss of muscle stem cells and reduced heterochromatin condensation in rare surviving satellite cells. Inactivation of Pax7 in Myf5-expressing cells revealed that the majority of adult muscle stem cells originate from myogenic lineages, which express the myogenic regulators Myf5 or MyoD. Likewise, the majority of muscle stem cells are replenished from Myf5-expressing myogenic cells during adult life, and inactivation of Pax7 in Myf5-expressing cells after muscle damage leads to a complete arrest of muscle regeneration. Finally, we demonstrate that a relatively small number of muscle stem cells are sufficient for efficient repair of skeletal muscles. We conclude that Pax7 acts at different levels in a nonhierarchical regulatory network controlling muscle-satellite-cell-mediated muscle regeneration.
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