Intramuscular adipose is derived from a non-Pax3 lineage and required for efficient regeneration of skeletal muscles.

Intramuscular adipose is derived from a non-Pax3 lineage and required for efficient regeneration of skeletal muscles.
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DOI:
10.1016/j.ydbio.2011.10.011
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发表时间:
2012-01-01
影响因子:
2.7
通讯作者:
Kuang S
Kuang S
中科院分区:
生物学3区
文献类型:
--
作者:
Liu W;Liu Y;Lai X;Kuang S

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脂肪在骨骼肌中的异位积累与肌肉萎缩、胰岛素抵抗和糖尿病有关。然而,出生后肌内脂肪的发育起源及其与肌肉组织的相互作用尚不清楚。我们在这里报告说,与快速EDL肌肉相比,慢速SOL肌肉更富含成脂祖细胞,形成脂肪的倾向更高。在小鼠中使用Cre/LoxP介导的谱系追踪,我们表明EDL和SOL肌肉中的肌内脂肪完全来自Pax 3 −非肌源性谱系。相反,肩胛间棕色脂肪来源于Pax 3+谱系。为了剖析脂肪和骨骼肌组织之间的相互作用,我们使用Myf 5-Cre和aP 2-Cre小鼠与ROSA 26-iDTR小鼠组合,以分别遗传地消融成肌细胞谱系和成脂细胞谱系。而消融肌细胞谱系促进成脂分化,消融脂肪细胞谱系令人惊讶地损害了急性损伤的骨骼肌的再生。这些结果揭示了组织特异性脂肪的显著异质性和肌内脂肪在骨骼肌再生中以前未被认识到的作用。
Ectopic accumulation of adipose in the skeletal muscle is associated with muscle wasting, insulin resistance and diabetes. However, the developmental origin of postnatal intramuscular adipose and its interaction with muscle tissue are unclear. We report here that compared to the fast EDL muscles, slow SOL muscles are more enriched with adipogenic progenitors and have higher propensity to form adipose. Using Cre/LoxP mediated lineage tracing in mice, we show that intramuscular adipose in both EDL and SOL muscles is exclusively derived from a Pax3− non-myogenic lineage. In contrast, inter-scapular brown adipose is derived from the Pax3+ lineage. To dissect the interaction between adipose and skeletal muscle tissues, we used Myf5-Cre and aP2-Cre mice in combination with ROSA26-iDTR mice to genetically ablate myogenic and adipogenic cell lineages, respectively. Whereas ablation of the myogenic cell lineage facilitated adipogenic differentiation, ablation of the adipogenic cell lineage surprisingly impaired the regeneration of acutely injured skeletal muscles. These results reveal striking heterogeneity of tissue-specific adipose and a previously unappreciated role of intramuscular adipose in skeletal muscle regeneration.
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