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Denervation Drives YAP/TAZ Activation in Muscular Fibro/Adipogenic Progenitors
oleh: Felipe S. Gallardo, Adriana Córdova-Casanova, Alexia Bock-Pereda, Daniela L. Rebolledo, Andrea Ravasio, Juan Carlos Casar, Enrique Brandan
Format: | Article |
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Diterbitkan: | MDPI AG 2023-03-01 |
Deskripsi
Loss of motoneuron innervation (denervation) is a hallmark of neurodegeneration and aging of the skeletal muscle. Denervation induces fibrosis, a response attributed to the activation and expansion of resident fibro/adipogenic progenitors (FAPs), i.e., multipotent stromal cells with myofibroblast potential. Using in vivo and in silico approaches, we revealed FAPs as a novel cell population that activates the transcriptional coregulators YAP/TAZ in response to skeletal muscle denervation. Here, we found that denervation induces the expression and transcriptional activity of YAP/TAZ in whole muscle lysates. Using the <i>Pdgfra</i><sup>H2B:EGFP/+</sup> transgenic reporter mice to trace FAPs, we demonstrated that denervation leads to increased YAP expression that accumulates within FAPs nuclei. Consistently, re-analysis of published single-nucleus RNA sequencing (snRNA-seq) data indicates that FAPs from denervated muscles have a higher YAP/TAZ signature level than control FAPs. Thus, our work provides the foundations to address the functional role of YAP/TAZ in FAPs in a neurogenic pathological context, which could be applied to develop novel therapeutic approaches for the treatment of muscle disorders triggered by motoneuron degeneration.