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PXD055921

PXD055921 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSubstrate Stiffness Dictates Unique Doxorubicin-induced Senescence-associated Secretory Phenotypes and Transcriptomic Signatures in Human Pulmonary Fibroblasts
DescriptionCells are subjected to dynamic mechanical environments which impart various forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells, leading to elevated tension in fibroblasts among other cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and SASP is not well understood. Here, we show that mechanical tension, modeled using cell culture substrate rigidity, influences senescent cell markers like SA-beta-gal and secretory phenotypes. Comparing human primary pulmonary fibroblasts (IMR-90) cultured on physiological (2 kPa), fibrotic (50 kPa), and plastic (3 GPa) substrates followed by senescence induction using doxorubicin, we identified unique high-stiffness-driven secretory protein profiles using mass spectrometry and transcriptomic signatures, both showing an enrichment in collagen proteins. Computational meta-analysis of human interstitial lung disease single-cell RNA sequencing datasets confirmed these genes are highly expressed in disease samples and strongly correlate with mechanotransduction and senescence-related pathways. Thus, mechanical forces shape cell senescence and their secretory phenotypes.
HostingRepositoryMassIVE
AnnounceDate2025-01-08
AnnouncementXMLSubmission_2025-01-08_16:23:13.606.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJoanna Bons
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentTripleTOF 6600; Orbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-09-16 18:25:16ID requested
12025-01-08 16:23:13announced
Publication List
no publication
Keyword List
submitter keyword: Senescence-associated secretory phenotype (SASP), Data-independent acquisition (DIA), Quantitative proteomics, Human pulmonary fibroblasts, Secretome
Contact List
Birgit Schilling
contact affiliationBuck Institute
contact emailbschilling@buckinstitute.org
lab head
Joanna Bons
contact affiliationBuck Institute for Research on Aging
contact emailjbons@buckinstitute.org
dataset submitter
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MassIVE dataset URI
Dataset FTP location
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