PXD040479-1

PXD040479 is an original dataset announced via ProteomeXchange.

Title	Development of a 3D fatty infiltration platform to model, at higher scale, the impact of LY2090314 compound on fibro/adipogenic progenitor adipogenic drift
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-06-13
AnnouncementXML	Submission_2023-06-13_05:51:08.277.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AlessioReggio
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-27 11:11:47	ID requested
⏵ 1	2023-06-13 05:51:08	announced
2	2023-11-14 09:01:10	announced	2023-11-14: Updated project metadata.
3	2024-10-22 05:47:56	announced	2024-10-22: Updated project metadata.

submitter keyword: LY2090314, FAPs, Duchenne Muscular Dystrophy,Adipogenesis, b-catenin

CesareGargioli
contact affiliation	University of Rome “Tor Vergata”, Rome, 00133, Italy
contact email	cesare.gargioli@uniroma2.it
lab head
AlessioReggio
contact affiliation	University of Rome Tor Vergata
contact email	alessio.reggio@uniroma2.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/06/PXD040479

PRIDE project URI

• PRIDE
  1. PXD040479
     1. Label: PRIDE project
     2. Name: Development of a 3D fatty infiltration platform to model, at higher scale, the impact of LY2090314 compound on fibro/adipogenic progenitor adipogenic drift