biostudies-literatureReggio AMinistero dell'Istruzione, dell'Università e della RicercaTelethonUniversita degli Studi di Roma Tor VergataMinistero dell'Istruzione, dell'Università e della RicercaAFM-TéléthonMuscular Dystrophy AssociationItalian Ministry of University and Research PRIN Funding Schemedmm049915https://www.ebi.ac.uk/biostudies/studies/S-EPMC10309591biostudies-literatureUnknown16(6)In human dystrophies, progressive muscle wasting is exacerbated by ectopic deposition of fat and fibrous tissue originating from fibro/adipogenic progenitors (FAPs). In degenerating muscles, the ability of these cells to promote successful healing is attenuated, and FAPs aberrantly expand and differentiate into adipocytes and fibroblasts. Thus, arresting the fibro/adipogenic fate of FAPs, without affecting their physiological role, represents a valuable therapeutic strategy for patients affected by muscle diseases. Here, using a panel of adipose progenitor cells, including human-derived FAPs, coupled with pharmacological perturbations and proteome profiling, we report that LY2090314 interferes with a genuine adipogenic program acting as WNT surrogate for the stabilization of a competent β-Disease models & mechanismsA 3D adipogenesis platform to study the fate of fibro/adipogenic progenitors in muscular dystrophies.PMC10309591968551MDA 96855123551201742SBXA_004TMPGMFU22TTGrumati PRainer ACirillo CCannata SFuoco CTesta SSeliktar DReggio ADe Paolis FBernardini SBousselmi SCicciarelli FGargioli CfalseA 3D adipogenesis platform to study the fate of fibro/adipogenic progenitors in muscular dystrophies.In human dystrophies, progressive muscle wasting is exacerbated by ectopic deposition of fat and fibrous tissue originating from fibro/adipogenic progenitors (FAPs). In degenerating muscles, the ability of these cells to promote successful healing is attenuated, and FAPs aberrantly expand and differentiate into adipocytes and fibroblasts. Thus, arresting the fibro/adipogenic fate of FAPs, without affecting their physiological role, represents a valuable therapeutic strategy for patients affected by muscle diseases. Here, using a panel of adipose progenitor cells, including human-derived FAPs, coupled with pharmacological perturbations and proteome profiling, we report that LY2090314 interferes with a genuine adipogenic program acting as WNT surrogate for the stabilization of a competent β-2023-01-01T00:00:00Z2023 Jun2026-05-28T08:51:09.689Z2025-02-19T01:18:09.827ZS-EPMC103095913727242810.1242/dmm.049915