Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution.

Prepubertal skeletal muscle growth requires Pax7-expressing satellite cell-derived myonuclear contribution.
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DOI:
10.1242/dev.167197
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发表时间:
2018-10-25
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Chakkalakal JV
Chakkalakal JV
中科院分区:
其他
文献类型:
--
作者:
Bachman JF;Klose A;Liu W;Paris ND;Blanc RS;Schmalz M;Knapp E;Chakkalakal JV

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表达Pax 7的卫星细胞(SC)在断奶后出生后骨骼肌发育中的功能作用仍然不清楚。因此,在青春期前生长,断奶后,但在青春期开始之前的一段时间,SC的相关性尚未得到研究。在这里,我们的特点是小鼠骨骼肌生长在青春期前,并发现显着增加肌纤维横截面积与SC衍生的肌纤维数量。值得注意的是,全基因组RNA测序分析确定,断奶后的青少年和早期青少年骨骼肌有显着不同的基因表达特征。这些区别是一致的广泛的骨骼肌成熟在这个重要的,虽然短暂的,发展阶段。用Pax 7 CreERT 2/+; Rosa 26 nTnG/+小鼠对SC进行的不褪色标记表明,在青春期前,SC来源的肌萎缩贡献,在青春期开始时大幅减少。在Pax 7 CreERT 2/+; Rosa 26 DTA/+小鼠中,青春期前的SC消耗减少了肌纤维的大小和肌纤维的数量,并在快速和缓慢收缩的肌肉中引起类似程度的力产生缺陷。总的来说,这些数据表明SC衍生的肌纤维增生作为一种细胞机制,有助于青春期前肥大骨骼肌的生长。总结:在青春期前小鼠骨骼肌的基因表达和形态学变化的检查表明,卫星细胞来源的肌纤维增生有助于青春期前肥大骨骼肌的生长。
The functional role of Pax7-expressing satellite cells (SCs) in postnatal skeletal muscle development beyond weaning remains obscure. Therefore, the relevance of SCs during prepubertal growth, a period after weaning but prior to the onset of puberty, has not been examined. Here, we have characterized mouse skeletal muscle growth during prepuberty and found significant increases in myofiber cross-sectional area that correlated with SC-derived myonuclear number. Remarkably, genome-wide RNA-sequencing analysis established that post-weaning juvenile and early adolescent skeletal muscle have markedly different gene expression signatures. These distinctions are consistent with extensive skeletal muscle maturation during this essential, albeit brief, developmental phase. Indelible labeling of SCs with Pax7CreERT2/+; Rosa26nTnG/+ mice demonstrated SC-derived myonuclear contribution during prepuberty, with a substantial reduction at puberty onset. Prepubertal depletion of SCs in Pax7CreERT2/+; Rosa26DTA/+ mice reduced myofiber size and myonuclear number, and caused force generation deficits to a similar extent in both fast and slow-contracting muscles. Collectively, these data demonstrate SC-derived myonuclear accretion as a cellular mechanism that contributes to prepubertal hypertrophic skeletal muscle growth. Summary: Examination of gene expression and morphological changes in mouse skeletal muscle during prepuberty demonstrates that satellite cell-derived myonuclear accretion contributes to prepubertal hypertrophic skeletal muscle growth.
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