Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation
Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation
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DOI：
10.1046/j.1432-0436.2001.680412.x
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发表时间：
2001-10-01
期刊：
影响因子：
2.9
通讯作者：
Rudnicki, MA
中科院分区：
文献类型：
--
作者：
Asakura, A;Komaki, M;Rudnicki, MA
肌肉卫星细胞被认为是一种负责骨骼肌出生后生长和再生的干细胞群。然而，观察到培养的成肌细胞分别在骨形态发生蛋白（BMPs）或脂肪生成诱导剂处理后分化为骨细胞或脂肪细胞，这表明在间充质谱系中存在一定程度的可塑性。为了进一步研究这一现象，我们探索了从成年小鼠分离的卫星细胞的成骨和成脂潜能。我们的实验清楚地表明，卫星细胞衍生的原代成肌细胞，表达MyoD、Myf5、Pax7和desmin等成肌标志物，分别在bmp或成脂诱导剂处理后只能分化为骨细胞或脂肪细胞。然而，在Matrigel中培养的分离肌纤维上的卫星细胞很容易分化为肌细胞以及成骨细胞和脂肪细胞，而原代成肌细胞则不能。从缺乏肌源性转录因子MyoD （MyoD-/-）的小鼠中分离的卫星细胞衍生的原代肌母细胞在体内和体外分化为肌细胞的能力较差（Megeney et al., Genes Dev. 1996; Sabourin et al.， J. Cell Biol.）。, 1999)。因此，我们测试了MyoD-/-原代成肌细胞是否比野生型细胞表现出更高的可塑性。出乎意料的是，与野生型细胞相比，MyoD-/-原代成肌细胞的成骨或成脂分化潜能没有增加。综上所述，这些结果强烈表明肌肉卫星细胞具有多能间充质干细胞活性，能够形成骨细胞、脂肪细胞以及肌细胞。
Muscle satellite cells are believed to represent a committed stem cell population that is responsible for the postnatal growth and regeneration of skeletal muscle. However, the observation that cultured myoblasts differentiate into osteocytes or adipocytes following treatment with bone morphogenetic proteins (BMPs) or adipogenic inducers, respectively, suggests some degree of plasticity within the mesenchymal lineage. To further investigate this phenomenon, we explore the osteogenic and adipogenic potential of satellite cells isolated from adult mice. Our experiments clearly demonstrate that satellite cell-derived primary myoblasts, expressing myogenic markers such as MyoD, Myf5, Pax7 and desmin, differentiated only into osteocytes or adipocytes following treatment with BMPs or adipogenic inducers, respectively. However, satellite cells on isolated muscle fibers cultured in Matrigel readily differentiated into myocytes as well as osteogenic and adipogenic lineages, whereas primary myoblasts did not. Satellite cell-derived primary myoblasts isolated from mice lacking the myogenic transcription factor MyoD (MyoD-/-) differentiate into myocytes poorly in vivo and in vitro (Megeney et al., Genes Dev. 1996; Sabourin et. al, J. Cell Biol., 1999). Therefore, we tested whether MyoD-/- primary myoblasts display increased plasticity relative to wild type cells. Unexpectedly, the osteogenic or adipogenic differentiation potential of MyoD-/- primary myoblasts did not increase compared to wild-type cells. Taken together, these results strongly suggest that muscle satellite cells possess multipotential mesenchymal stem cell activity and are capable of forming osteocytes and adipocytes as well as myocytes.