A Tead1-Apelin axis directs paracrine communication from myogenic to endothelial cells in skeletal muscle.
A Tead1-Apelin axis directs paracrine communication from myogenic to endothelial cells in skeletal muscle.
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DOI：
10.1016/j.isci.2022.104589
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发表时间：
2022-07-15
期刊：
影响因子：
5.8
通讯作者：
Feige, Jerome N.
中科院分区：
文献类型：
--
作者：
Lee, Umji;Stuelsatz, Pascal;Karaz, Sonia;McKellar, David W.;Russeil, Julie;Deak, Maria;De Vlaminck, Iwijn;Lepper, Christoph;Deplancke, Bart;Cosgrove, Benjamin D.;Feige, Jerome N.
Apelin（Apln）是一种调节骨骼肌可塑性和代谢的肌因子，在衰老过程中下降。通过酵母单杂交转录因子结合筛选，我们确定了TEA结构域转录因子1（Tead 1）作为一种新的调节Apln启动子。再生肌肉的单细胞分析显示，爱帕琳受体（Aplnr）富集在内皮细胞中，而Tead 1富集在肌原细胞中。敲低Tead 1在体外刺激肌细胞分泌Apln，肌纤维特异性过表达Tead 1在体内抑制Apln分泌。通过Tead 1敲低肌肉细胞中的Apln分泌通过内皮Aplnr刺激内皮细胞扩增。在体内，Apln肽补充增强内皮细胞扩增，而Tead 1肌肉过表达延迟肌肉损伤后的内皮重塑。我们的工作描述了一种新的旁分泌串扰，其中Apln的分泌是由Tead 1在肌原细胞中控制的，并影响肌肉修复过程中的内皮重塑。转录因子结合筛选确定Tead 1结合Apln启动子Tead 1抑制Apln肽从肌源性细胞的分泌Apln在肌肉再生期间刺激内皮细胞重塑Tead 1介导的肌源性细胞中Apln的调节控制内皮细胞重塑分子生物学;基因调控的分子机制;细胞生物学
Apelin (Apln) is a myokine that regulates skeletal muscle plasticity and metabolism and declines during aging. Through a yeast one-hybrid transcription factor binding screen, we identified the TEA domain transcription factor 1 (Tead1) as a novel regulator of the Apln promoter. Single-cell analysis of regenerating muscle revealed that the apelin receptor (Aplnr) is enriched in endothelial cells, whereas Tead1 is enriched in myogenic cells. Knock-down of Tead1 stimulates Apln secretion from muscle cells in vitro and myofiber-specific overexpression of Tead1 suppresses Apln secretion in vivo. Apln secretion via Tead1 knock-down in muscle cells stimulates endothelial cell expansion via endothelial Aplnr. In vivo, Apln peptide supplementation enhances endothelial cell expansion while Tead1 muscle overexpression delays endothelial remodeling following muscle injury. Our work describes a novel paracrine crosstalk in which Apln secretion is controlled by Tead1 in myogenic cells and influences endothelial remodeling during muscle repair. A transcription factor binding screen identified that Tead1 binds the Apln promoter Tead1 represses the secretion of the Apln peptide from myogenic cells Apln stimulates endothelial cell remodeling during muscle regeneration Tead1-mediated regulation of Apln in myogenic cells controls endothelial cell remodeling Molecular biology; Molecular mechanism of gene regulation; Cell biology
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