PXD015728-1

PXD015728 is an original dataset announced via ProteomeXchange.

Title	Deep proteome of aging skeletal muscles reveals Smoc2 as a modulator of satellite cell regenerative capacity
Description	During aging, the number and functionality of muscle stem cells (MuSCs) decreases leading to impaired regeneration of aged skeletal muscle. In addition to intrinsic changes in aged MuSCs, extracellular matrix (ECM) proteins deriving from other cell types, e.g., fibrogenic-adipogenic progenitor cells (FAPs), contribute to the aging phenotype of MuSCs and impaired regeneration in the elderly. So far, no comprehensive analysis on how age-dependent changes in the whole skeletal muscle proteome affect MuSC function have been conducted. Here, we investigated age-dependent changes in the proteome of different skeletal muscle types by applying deep quantitative mass spectrometry. We identified 183 extracellular matrix proteins that show different abundances in skeletal muscles of old mice. By integrating single cell sequencing data, we reveal that transcripts of those ECM proteins are mainly expressed in FAPs, suggesting that FAPs are the main contributors to ECM remodelling during aging. We functionally investigated one of those ECM molecules, namely Smoc2, which is aberrantly expressed during aging. We show that Smoc2 levels are elevated during regeneration and that its accumulation in the aged MuSC niche causes impairment of MuSCs function through constant activation of integrin/MAPK signaling. In vivo, supplementation of exogenous Smoc2 hampers the regeneration of young muscles following serial injuries, leading to a phenotype reminiscent of regenerating aged skeletal muscle. Taken together, we provide a comprehensive resource of changes in the composition of the ECM of aged skeletal muscles, we pinpoint the cell types driving these changes, and we identify a new niche protein causing functional impairment of MuSCs thereby hampering the regeneration capacity of skeletal muscles.
HostingRepository	PRIDE
AnnounceDate	2021-11-25
AnnouncementXML	Submission_2021-11-25_06:52:28.756.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alessandro Ori
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-07 04:45:41	ID requested
⏵ 1	2021-11-25 06:52:29	announced
2	2024-10-22 05:30:27	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: muscle stem cell, aging, regeneration, Smoc2, satellite cell, skeletal muscle, proteomics, extracellular matrix

Alessandro Ori
contact affiliation	Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) Beutenbergstr. 11 07745 Jena Germany Tel.: +49-3641-656831
contact email	Alessandro.Ori@leibniz-fli.de
lab head
Alessandro Ori
contact affiliation	Leibniz Institute on Aging
contact email	aleori@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015728
     1. Label: PRIDE project
     2. Name: Deep proteome of aging skeletal muscles reveals Smoc2 as a modulator of satellite cell regenerative capacity