Shefer Gabi, Wleklinski-Lee Monika, Yablonka-Reuveni Zipora
Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195, USA.
J Cell Sci. 2004 Oct 15;117(Pt 22):5393-404. doi: 10.1242/jcs.01419. Epub 2004 Oct 5.
We show that muscle satellite cells, traditionally considered as committed myogenic precursors, are comprised of Pax7-expressing progenitors that preserve a mesenchymal repertoire extending beyond a mere myogenic potential. Mouse satellite cells from freshly isolated single myofibers, cultured individually in serum-rich growth medium, produced myogenic and non-myogenic clones. Only the myogenic clones expressed muscle-specific transcription factors and formed myotubes. Pax7 was initially expressed in all clones, but subsequently was associated only with the myogenic clones. Some cells in the non-myogenic clones expressed alpha-smooth muscle actin and nestin whereas others differentiated into mature adipocytes. This type of cell composition mirrors characteristics of mesenchymal stem cell progeny. Overall, individual myofibers persistently gave rise to both clonal phenotypes, but the ratio of myogenic to non-myogenic clones randomly varied among fibers. This randomness indicates that clonal dichotomy reflects satellite cell suppleness rather than pre-fated cell heterogeneity. We conclude that satellite cells possess mesenchymal plasticity, being able to commit either to myogenesis or to a mesenchymal alternative differentiation (MAD) program.
我们发现，传统上被认为是定向肌源性前体细胞的肌肉卫星细胞，由表达Pax7的祖细胞组成，这些祖细胞保留了一种间充质细胞库，其功能远不止单纯的肌源性潜能。从新鲜分离的单个肌纤维中获取的小鼠卫星细胞，在富含血清的生长培养基中单独培养，产生了肌源性和非肌源性克隆。只有肌源性克隆表达肌肉特异性转录因子并形成肌管。Pax7最初在所有克隆中表达，但随后仅与肌源性克隆相关。非肌源性克隆中的一些细胞表达α-平滑肌肌动蛋白和巢蛋白，而其他细胞则分化为成熟脂肪细胞。这种细胞组成类型反映了间充质干细胞后代的特征。总体而言，单个肌纤维持续产生两种克隆表型，但肌源性克隆与非肌源性克隆的比例在不同纤维之间随机变化。这种随机性表明克隆二分法反映了卫星细胞的灵活性，而非预先确定的细胞异质性。我们得出结论，卫星细胞具有间充质可塑性，能够定向分化为肌生成或间充质替代分化（MAD）程序。
