Fibroadipogenic Progenitors Regulate the Basal Proliferation of Satellite Cells and Homeostasis of Pharyngeal Muscles via HGF Secretion

纤维脂肪生成祖细胞通过 HGF 分泌调节卫星细胞的基础增殖和咽肌的稳态

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作者:Eunhye Kim, Fang Wu, Danbi Lim, Christopher Zeuthen, Yiming Zhang, James Allen, Laura Muraine, Capucine Trollet, Katherine E Vest, Hyojung J Choo

Abstract

Skeletal muscle stem cells, known as satellite cells (SCs), are quiescent in normal adult limb muscles. Injury stimulates SC proliferation, differentiation, and fusion to regenerate muscle structure. In pharyngeal muscles, which are critical for swallowing foods and liquids, SCs proliferate and fuse in the absence of injury. It is unknown what factors drive increased basal activity of pharyngeal SCs. Here, we determined how niche factors influence the status of pharyngeal versus limb SCs. In vivo, a subset of pharyngeal SCs present features of activated SCs, including large cell size and increased mitochondrial content. In this study, we discovered that the pharyngeal muscle contains high levels of active hepatocyte growth factor (HGF), which is known to activate SCs in mice and humans. We found that fibroadipogenic progenitors (FAPs) are the major cell type providing HGF and are thus responsible for basal proliferation of SCs in pharyngeal muscles. Lastly, we confirmed the critical role of FAPs for pharyngeal muscle function and maintenance. This study gives new insights to explain the distinctive SC activity of pharyngeal muscles.

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