Shinin Vasily, Gayraud-Morel Barbara, Gomès Danielle, Tajbakhsh Shahragim
Stem Cells and Development, Department of Developmental Biology, Pasteur Institute, CNRS URA 2578, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Nat Cell Biol. 2006 Jul;8(7):677-87. doi: 10.1038/ncb1425. Epub 2006 Jun 25.
Satellite cells assure postnatal skeletal muscle growth and repair. Despite extensive studies, their stem cell character remains largely undefined. Using pulse-chase labelling with BrdU to mark the putative stem cell niche, we identify a subpopulation of label-retaining satellite cells during growth and after injury. Strikingly, some of these cells display selective template-DNA strand segregation during mitosis in the muscle fibre in vivo, as well as in culture independent of their niche, indicating that genomic DNA strands are nonequivalent. Furthermore, we demonstrate that the asymmetric cell-fate determinant Numb segregates selectively to one daughter cell during mitosis and before differentiation, suggesting that Numb is associated with self-renewal. Finally, we show that template DNA cosegregates with Numb in label-retaining cells that express the self-renewal marker Pax7. The cosegregation of 'immortal' template DNA strands and their link with the asymmetry apparatus has important implications for stem cell biology and cancer.
卫星细胞确保出生后骨骼肌的生长和修复。尽管进行了广泛的研究，但其干细胞特性在很大程度上仍不明确。我们使用BrdU进行脉冲追踪标记以标记假定的干细胞生态位，在生长过程中和损伤后识别出一群标记保留卫星细胞。令人惊讶的是，这些细胞中的一些在体内肌纤维的有丝分裂过程中以及在与生态位无关的培养中表现出选择性模板DNA链分离，这表明基因组DNA链是不等价的。此外，我们证明不对称细胞命运决定因子Numb在有丝分裂期间和分化之前选择性地分离到一个子细胞中，这表明Numb与自我更新有关。最后，我们表明模板DNA在表达自我更新标记Pax7的标记保留细胞中与Numb共分离。“不朽”模板DNA链的共分离及其与不对称机制的联系对干细胞生物学和癌症具有重要意义。
