Department of Biological Structure, Box 357420, Warren B Magneson Health Sciences Building, 1959 NE Pacific Street, University of Washington School of Medicine, Seattle, WA 98195, USA.
Dev Biol. 2010 Apr 15;340(2):330-43. doi: 10.1016/j.ydbio.2010.01.006. Epub 2010 Jan 15.
Satellite cells are myogenic progenitors that reside on the myofiber surface and support skeletal muscle repair. We used mice in which satellite cells were detected by GFP expression driven by nestin gene regulatory elements to define age-related changes in both numbers of satellite cells that occupy hindlimb myofibers and their individual performance. We demonstrate a reduction in satellite cells per myofiber with age that is more prominent in females compared to males. Satellite cell loss also persists with age in myostatin-null mice regardless of increased muscle mass. Immunofluorescent analysis of isolated myofibers from nestin-GFP/Myf5(nLacZ/+) mice reveals a decline with age in the number of satellite cells that express detectable levels of betagal. Nestin-GFP expression typically diminishes in primary cultures of satellite cells as myogenic progeny proliferate and differentiate, but GFP subsequently reappears in the Pax7(+) reserve population. Clonal analysis of sorted GFP(+) satellite cells from hindlimb muscles shows heterogeneity in the extent of cell density and myotube formation among colonies. Reserve cells emerge primarily within high-density colonies, and the number of clones that produce reserve cells is reduced with age. Thus, satellite cell depletion with age could be attributed to a reduced capacity to generate a reserve population.
卫星细胞是存在于肌纤维表面的成肌祖细胞，能支持骨骼肌修复。我们使用由巢蛋白基因调控元件驱动 GFP 表达来检测卫星细胞的小鼠，以确定占据后肢肌纤维的卫星细胞数量及其个体性能的年龄相关性变化。我们证明，随着年龄的增长，每个肌纤维的卫星细胞数量减少，而雌性小鼠比雄性小鼠更为明显。无论肌肉质量增加如何，肌肉生长抑制素缺失的小鼠的卫星细胞丢失也会随着年龄的增长而持续存在。从 nestin-GFP/Myf5(nLacZ/+) 小鼠的分离肌纤维的免疫荧光分析显示，表达可检测水平的 betagal 的卫星细胞数量随年龄的增长而下降。nestin-GFP 表达通常在卫星细胞的原代培养中随着成肌前体的增殖和分化而减少，但 GFP 随后会在 Pax7(+)储备群体中重新出现。从后肢肌肉分选的 GFP(+)卫星细胞的克隆分析显示，在细胞密度和肌管形成方面，克隆之间存在异质性。储备细胞主要出现在高密度克隆中，随着年龄的增长，产生储备细胞的克隆数量减少。因此，随着年龄的增长，卫星细胞耗竭可能归因于产生储备群体的能力降低。
