<?xml version="1.0" encoding="UTF-8" standalone="yes"?> <ProteomeXchangeDataset id="PXD013241" formatVersion="1.4.0" xsi:noNamespaceSchemaLocation="proteomeXchange-1.4.0.xsd" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <CvList> <Cv fullName="PSI-MS" uri="https://raw.githubusercontent.com/HUPO-PSI/psi-ms-CV/master/psi-ms.obo" id="MS"/> <Cv fullName="PSI-MOD" uri="https://raw.githubusercontent.com/MICommunity/psidev/master/psi/mod/data/PSI-MOD.obo" id="MOD"/> <Cv fullName="UNIMOD" uri="http://www.unimod.org/obo/unimod.obo" id="UNIMOD"/> </CvList> <ChangeLog> <ChangeLogEntry date="2024-10-22">Updated project metadata.</ChangeLogEntry> </ChangeLog> <DatasetSummary announceDate="2024-10-22" hostingRepository="PRIDE" title="Secreted proteins extracted (3M NaCl) from EP/LP MSCs grown on soft/stiff substrates for 8 days"> <Description>Tissues are maintained by homeostatic feedback mechanisms in which cells can respond to, but also modify, the chemical and mechanical properties of the surrounding extracellular matrix (ECM). Mechano-sensitive mesenchymal stem cells (MSCs) resident in the marrow niche experience a diverse mechanical environment, but ageing can affect the composition and quality of bone and marrow tissues. Here we quantified the compounded effects of substrate stiffness and replication-induced senescence on MSC morphology and their ability to modify their environments through secretion of ECM proteins. The ECM proteome was found to be sensitive to substrate stiffness, but pharmacological inhibition of cellular contractility perturbed this response, decreasing levels of tenascin-C, fibulins and fibronectin. A corresponding change in the ECM of senescent cells, concomitant with a loss of mechano-responsive morphological features, suggested a decoupling of mechanotransduction pathways. Intracellular proteomic and transcriptomic analyses confirmed a decrease in all components of the cytoskeletal protein homeostasis machinery in senescent MSCs. These results demonstrate a senescence-mediated perturbation to cytoskeletal homeostasis, pathways of mechanotransduction and the secretion of ECM proteins considered necessary for tissue maintenance.</Description> <ReviewLevel> <cvParam cvRef="MS" accession="MS:1002854" name="Peer-reviewed dataset"/> </ReviewLevel> <RepositorySupport> <cvParam cvRef="MS" accession="MS:1002857" name="Unsupported dataset by repository"/> </RepositorySupport> </DatasetSummary> <DatasetIdentifierList> <DatasetIdentifier> <cvParam cvRef="MS" accession="MS:1001919" name="ProteomeXchange accession number" value="PXD013241"/> <cvParam cvRef="MS" accession="MS:1001921" name="ProteomeXchange accession number version number" value="2"/> </DatasetIdentifier> </DatasetIdentifierList> <DatasetOriginList> <DatasetOrigin> <cvParam cvRef="MS" accession="MS:1002868" name="Original data"/> </DatasetOrigin> </DatasetOriginList> <SpeciesList> <Species> <cvParam cvRef="MS" accession="MS:1001469" name="taxonomy: scientific name" value="Homo sapiens (Human)"/> <cvParam cvRef="MS" accession="MS:1001467" name="taxonomy: NCBI TaxID" value="9606"/> </Species> </SpeciesList> <InstrumentList> <Instrument id="Instrument_1"> <cvParam cvRef="MS" accession="MS:1001910" name="LTQ Orbitrap Elite"/> </Instrument> </InstrumentList> <ModificationList> <cvParam cvRef="MOD" accession="MOD:00696" name="phosphorylated residue"/> <cvParam cvRef="MOD" accession="MOD:00425" name="monohydroxylated residue"/> <cvParam cvRef="MOD" accession="MOD:00397" name="iodoacetamide derivatized residue"/> </ModificationList> <ContactList> <Contact id="project_submitter"> <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Venkatesh Mallikarjun"/> <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="vm9uq@virginia.edu"/> <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="University of Manchester"/> <cvParam cvRef="MS" accession="MS:1002037" name="dataset submitter"/> </Contact> <Contact id="project_lab_head"> <cvParam cvRef="MS" accession="MS:1002332" name="lab head"/> <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Joe Swift"/> <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="joe.swift@manchester.ac.uk"/> <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="Division of Cell Matrix Biology & Regenerative Medicine (L5) / Division of Cell Matrix Biology & Regenerative Medicine"/> </Contact> </ContactList> <PublicationList> <Publication id="pending"> <cvParam cvRef="MS" accession="MS:1002858" name="Dataset with its publication pending"/> </Publication> </PublicationList> <KeywordList> <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="Senescence, MSC, ageing, stiffness"/> <cvParam cvRef="MS" accession="MS:1001926" name="curator keyword" value="Biological"/> </KeywordList> <FullDatasetLinkList> <FullDatasetLink> <cvParam cvRef="MS" accession="MS:1002852" name="Dataset FTP 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