摘要：SummaryApelin (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 theAplnpromoter. Single-cell analysis of regenerating muscle revealed that the apelin receptor (Aplnr) is enriched in endothelial cells, whereasTead1is enriched in myogenic cells. Knock-down ofTead1stimulates Apln secretion from muscle cellsin vitroand myofiber-specific overexpression ofTead1suppresses Apln secretionin vivo. Apln secretion viaTead1knock-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.Graphical abstractDisplay OmittedHighlights•A transcription factor binding screen identified that Tead1 binds theAplnpromoter•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 remodelingMolecular biology; Molecular mechanism of gene regulation; Cell biology
