Denervation Drives YAP/TAZ Activation in Muscular Fibro/Adipogenic Progenitors

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dc.contributor.authorGallardo, Felipe S.
dc.contributor.authorCordova-Casanova, Adriana
dc.contributor.authorBock-Pereda, Alexia
dc.contributor.authorRebolledo, Daniela L.
dc.contributor.authorRavasio, Andrea
dc.contributor.authorCasar, Juan Carlos
dc.contributor.authorBrandan, Enrique
dc.date.accessioned2025-01-20T20:16:14Z
dc.date.available2025-01-20T20:16:14Z
dc.date.issued2023
dc.description.abstractLoss 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 Pdgfra(H2B:EGFP/+) 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.
dc.fuente.origenWOS
dc.identifier.doi10.3390/ijms24065585
dc.identifier.eissn1422-0067
dc.identifier.urihttps://doi.org/10.3390/ijms24065585
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92316
dc.identifier.wosidWOS:000959148900001
dc.issue.numero6
dc.language.isoen
dc.revistaInternational journal of molecular sciences
dc.rightsacceso restringido
dc.subjectdenervation
dc.subjectskeletal muscle
dc.subjectYAP
dc.subjectTAZ
dc.subjectFAPs
dc.subjectfibrosis
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDenervation Drives YAP/TAZ Activation in Muscular Fibro/Adipogenic Progenitors
dc.typeartículo
dc.volumen24
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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