Schienda Jaclyn, Engleka Kurt A, Jun Susan, Hansen Mark S, Epstein Jonathan A, Tabin Clifford J, Kunkel Louis M, Kardon Gabrielle
Howard Hughes Medical Institute, Program in Genomics, Children's Hospital, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):945-50. doi: 10.1073/pnas.0510164103. Epub 2006 Jan 17.
Repair of mature skeletal muscle is mediated by adult muscle progenitors. Satellite cells have long been recognized as playing a major role in muscle repair, whereas side population (SP) cells have more recently been identified as contributing to this process. The developmental source of these two progenitor populations has been considerably debated. We explicitly tested and quantified the contribution of embryonic somitic cells to these progenitor populations. Chick somitic cells were labeled by using replication-defective retroviruses or quail/chick chimeras, and mouse cells were labeled by crossing somite-specific, Pax3-derived Cre driver lines with a Cre-dependent reporter line. We show that the majority of, if not all, limb muscle satellite cells arise from cells expressing Pax3 specifically in the hypaxial somite and their migratory derivatives. We also find that a significant number of, but not all, limb muscle SP cells are derived from the hypaxial somite. Notably, the heterogeneity in the developmental origin of SP cells is reflected in their functional heterogeneity; somitically derived SP cells are intrinsically more myogenic than nonsomitically derived ones. Thus, we show that the somites, which supply embryonic and fetal myoblasts, are also an important source of highly myogenic adult muscle progenitors.
成熟骨骼肌的修复由成体肌肉祖细胞介导。长期以来,卫星细胞一直被认为在肌肉修复中起主要作用,而侧群(SP)细胞最近才被确定参与这一过程。这两种祖细胞群体的发育来源一直存在很大争议。我们明确测试并量化了胚胎体节细胞对这些祖细胞群体的贡献。通过使用复制缺陷型逆转录病毒或鹌鹑/鸡嵌合体对鸡体节细胞进行标记,通过将体节特异性、源自Pax3的Cre驱动系与Cre依赖性报告系杂交对小鼠细胞进行标记。我们发现,大多数(如果不是全部)肢体肌肉卫星细胞源自特异性表达Pax3的轴下肌节及其迁移衍生物中的细胞。我们还发现,相当数量(但不是全部)的肢体肌肉SP细胞源自轴下肌节。值得注意的是,SP细胞发育起源的异质性反映在它们的功能异质性上;源自体节的SP细胞在本质上比非源自体节的细胞更具成肌性。因此,我们表明,提供胚胎和胎儿成肌细胞的体节也是高成肌性成体肌肉祖细胞的重要来源。