| Autor: |
Gallardo FS; Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.; Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Santiago 7750000, Chile., Córdova-Casanova A; Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.; Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Santiago 7750000, Chile., Bock-Pereda A; Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.; Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Santiago 7750000, Chile., Rebolledo DL; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas 6213515, Chile., Ravasio A; Institute for Biological and Medical Engineering, School of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile., Casar JC; Departamento de Neurología, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile., Brandan E; Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.; Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Santiago 7750000, Chile.; Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago 7510602, Chile. |
| Abstrakt: |
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 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. |
