Myogenic specification of side population cells in skeletal muscle.
Myogenic specification of side population cells in skeletal muscle.
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DOI：
10.1083/jcb.200202092
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发表时间：
2002-10-14
影响因子：
7.8
通讯作者：
Rudnicki, Michael A
中科院分区：
文献类型：
--
作者：
Asakura, Atsushi;Seale, Patrick;Girgis-Gabardo, Adele;Rudnicki, Michael A
骨骼肌包含被称为卫星细胞的肌源性前体细胞和肌肉来源的干细胞，这些干细胞被认为是多能的。我们进一步研究了肌源性干细胞和卫星细胞的分化潜能，以阐明这两类细胞之间的关系。FACS®对肌肉来源干细胞的一部分-肌肉侧群体(SP)细胞的分析显示，表达了造血干细胞标记SCA-1，但没有发现任何卫星细胞标记的表达。肌肉中的SP细胞大大丰富，使其具有形成造血祖细胞的能力。此外，具有造血潜能的肌肉SP细胞呈CD45阳性。然而，肌肉SP细胞在体外不能分化为肌细胞。相反，卫星细胞产生心肌细胞，但不表达SCA-1和CD45，也不形成造血集落。重要的是，肌肉SP细胞在肌肉内移植后显示出同时产生肌细胞和卫星细胞的潜力。此外，肌肉SP细胞在与成肌细胞共培养后进行了肌源性分化。与成肌细胞共培养或强制表达MyoD也可以诱导缺乏Pax7基因的小鼠肌肉SP细胞的肌肉分化。Pax7基因是卫星细胞发育的关键基因。因此，这些数据证明了卫星细胞和肌源性干细胞代表着不同的群体，并证明了肌源性干细胞具有通过肌细胞介导的诱导相互作用产生肌源性细胞的潜力。
Skeletal muscle contains myogenic progenitors called satellite cells and muscle-derived stem cells that have been suggested to be pluripotent. We further investigated the differentiation potential of muscle-derived stem cells and satellite cells to elucidate relationships between these two populations of cells. FACS® analysis of muscle side population (SP) cells, a fraction of muscle-derived stem cells, revealed expression of hematopoietic stem cell marker Sca-1 but did not reveal expression of any satellite cell markers. Muscle SP cells were greatly enriched for cells competent to form hematopoietic colonies. Moreover, muscle SP cells with hematopoietic potential were CD45 positive. However, muscle SP cells did not differentiate into myocytes in vitro. By contrast, satellite cells gave rise to myocytes but did not express Sca-1 or CD45 and never formed hematopoietic colonies. Importantly, muscle SP cells exhibited the potential to give rise to both myocytes and satellite cells after intramuscular transplantation. In addition, muscle SP cells underwent myogenic specification after co-culture with myoblasts. Co-culture with myoblasts or forced expression of MyoD also induced muscle differentiation of muscle SP cells prepared from mice lacking Pax7 gene, an essential gene for satellite cell development. Therefore, these data document that satellite cells and muscle-derived stem cells represent distinct populations and demonstrate that muscle-derived stem cells have the potential to give rise to myogenic cells via a myocyte-mediated inductive interaction.