Proteomics

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Development of a 3D fatty infiltration platform to model, at higher scale, the impact of LY2090314 compound on fibro/adipogenic progenitor adipogenic drift


ABSTRACT: In human dystrophies, the 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 adjuvate a successful healing is attenuated and FAPs aberrantly expand and differentiate into adipocytes and fibroblasts. Thus, arresting the fibroadipogenic 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 -catenin transcriptional complex. To predict the beneficial impact of LY2090314 in limiting ectopic deposition of fat in human muscles, we combined the Poly-Ethylene-Glycol-Fibrinogen biomimetic matrix with these progenitor cells to create a miniaturized 3D model of adipogenesis. Using this scalable system, we demonstrated that a two-digit nanomolar dose of this compound is effective to repress adipogenesis in a higher 3D scale, thus offering a concrete proof for the use of LY2090314 to limit FAP-derived fat infiltrates in dystrophic muscles.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Alessio Reggio  

LAB HEAD: Cesare Gargioli

PROVIDER: PXD040479 | Pride | 2023-06-13

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
2022-12-12_PG_AR_CTRL_1.raw Raw
2022-12-12_PG_AR_CTRL_2.raw Raw
2022-12-12_PG_AR_CTRL_3.raw Raw
2022-12-12_PG_AR_EXP_1.raw Raw
2022-12-12_PG_AR_EXP_2.raw Raw
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