Odd skipped-related 1 identifies a population of embryonic fibro-adipogenic progenitors regulating myogenesis during limb development.

Odd skipped-related 1 identifies a population of embryonic fibro-adipogenic progenitors regulating myogenesis during limb development.
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DOI:
10.1038/s41467-017-01120-3
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发表时间:
2017-10-31
影响因子:
16.6
通讯作者:
Stricker S
Stricker S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Vallecillo-García P;Orgeur M;Vom Hofe-Schneider S;Stumm J;Kappert V;Ibrahim DM;Börno ST;Hayashi S;Relaix F;Hildebrandt K;Sengle G;Koch M;Timmermann B;Marazzi G;Sassoon DA;Duprez D;Stricker S

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成纤维脂肪祖细胞(FAP)是成体骨骼肌中支持肌肉再生的间质细胞群。在发育过程中,间质肌结缔组织(MCT)细胞支持适当的肌肉模式,然而,其潜在的分子机制尚未得到很好的理解,并且仍然不清楚成人FAP和胚胎MCT细胞是否具有共同的谱系。我们在这里表明,小鼠胚胎肢MCT细胞表达转录因子Osr1,分化成纤维细胞和脂肪细胞在体内和体外定义的胚胎FAP样人口。遗传谱系追踪显示,发育中的Osr1+细胞产生一个成年FAP的子集。Osr1功能的丧失导致肌源性祖细胞增殖和存活的减少,从而导致肢体肌肉图案缺陷。转录组和功能分析显示,Osr1+细胞通过产生MCT特异性细胞外基质组分和分泌的信号传导因子提供关键的促肌生成生态位。成纤维脂肪祖细胞(FAP)形成成人间质肌结缔组织(MCT)的一部分,但这种非肌源性谱系的起源尚不清楚。在这里,作者表明,小鼠中的Odd skipped related 1(Osr1)标志着胚胎MCT,引起FAP,肢体中Osr1的缺失导致肌肉缺陷。
Fibro-adipogenic progenitors (FAPs) are an interstitial cell population in adult skeletal muscle that support muscle regeneration. During development, interstitial muscle connective tissue (MCT) cells support proper muscle patterning, however the underlying molecular mechanisms are not well understood and it remains unclear whether adult FAPs and embryonic MCT cells share a common lineage. We show here that mouse embryonic limb MCT cells expressing the transcription factor Osr1, differentiate into fibrogenic and adipogenic cells in vivo and in vitro defining an embryonic FAP-like population. Genetic lineage tracing shows that developmental Osr1+ cells give rise to a subset of adult FAPs. Loss of Osr1 function leads to a reduction of myogenic progenitor proliferation and survival resulting in limb muscle patterning defects. Transcriptome and functional analyses reveal that Osr1+ cells provide a critical pro-myogenic niche via the production of MCT specific extracellular matrix components and secreted signaling factors. Fibro-adipogenic progenitors (FAPs) form part of interstitial muscle connective tissue (MCT) in adults but the origin of this non-myogenic lineage is unclear. Here, the authors show that Odd skipped related 1 (Osr1) in mice marks embryonic MCT, giving rise to FAPs, and loss of Osr1 in the limb causes muscle defects.
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