The depletion of skeletal muscle satellite cells with age is concomitant with reduced capacity of single progenitors to produce reserve progeny
The depletion of skeletal muscle satellite cells with age is concomitant with reduced capacity of single progenitors to produce reserve progeny
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DOI：
10.1016/j.ydbio.2010.01.006
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发表时间：
2010-04-15
影响因子：
2.7
通讯作者：
Yablonka-Reuveni, Zipora
中科院分区：
文献类型：
--
作者：
Day, Kenneth;Shefer, Gabi;Yablonka-Reuveni, Zipora
卫星细胞是位于肌纤维表面并支持骨骼肌修复的肌源性祖细胞。我们使用的小鼠，其中卫星细胞检测到由巢蛋白基因调控元件驱动的GFP表达，以确定与年龄相关的变化，在两个卫星细胞占据后肢肌纤维和他们的个人表现。我们证明了随着年龄的增长，每个肌纤维的卫星细胞减少，这在女性中比男性更突出。无论肌肉质量增加与否，肌生长抑制素缺失小鼠的卫星细胞损失也随着年龄的增长而持续存在。从nestin-GFP/Myf 5（nLacZ/+）小鼠分离的肌纤维的免疫荧光分析揭示了表达可检测水平的β gal的卫星细胞的数量随着年龄的增长而下降。Nestin-GFP表达在卫星细胞的原代培养物中随着肌源性后代的增殖和分化而典型地减少，但是GFP随后在Pax 7（+）储备群体中重新出现。从后肢肌肉中分选的GFP（+）卫星细胞的克隆分析显示，克隆间细胞密度和肌管形成程度的异质性。储备细胞主要出现在高密度集落中，产生储备细胞的克隆数量随着年龄的增长而减少。因此，随着年龄的增长，卫星细胞的耗竭可能是由于产生储备种群的能力降低。(C)2010年爱思唯尔公司All rights reserved.
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 beta gal. 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. (C) 2010 Elsevier Inc. All rights reserved.