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PXD056100

PXD056100 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA comprehensive multi-omics signature of doxorubicin-induced cellular senescence in the postmenopausal human ovary
DescriptionA major aging hallmark is the accumulation of cellular senescence burden. Over time senescent cells contribute to tissue deterioration through chronic inflammation and fibrosis driven by the Senescence-Associated Secretory Phenotype (SASP). The human ovary is one of the first organs to age, and prominent age-related fibroinflammation within the ovarian microenvironment is consistent with the presence of senescent cells. However, bona fide senescent cells have not been validated in the human ovary. Therefore, we established a doxorubicin-induced model of cellular senescence to define a signature of ovarian senescent cells. Explants of human postmenopausal ovarian cortex and medulla were treated with doxorubicin for 24 hours followed by culture for up to 10 days in doxorubicin-free medium. Tissue viability was confirmed by histology, lack of apoptosis, and continued glucose consumption by explants. Single nuclei sequencing and proteomics revealed an unbiased signature of ovarian senescence. We identified distinct senescence profiles for the cortex and medulla, driven predominantly by epithelial and stromal cells. Proteomics uncovered subregional differences in addition to 120 proteins common to the cortex and medulla SASP. Integration of transcriptomic and proteomic analyses revealed 26 shared markers, defining a robust senotype of doxorubicin-induced senescence unique to the postmenopausal ovary. A subset of these proteins - Lumican, SOD2, MYH9 , and Periostin - were mapped onto native tissue to reveal compartment-specific localization. This senotype will help determine the role of cellular senescence in ovarian aging and inform the development of biomarkers to identify and therapeutic applications to slow or reverse ovarian aging, senescence, and cancer.
HostingRepositoryMassIVE
AnnounceDate2025-05-13
AnnouncementXMLSubmission_2025-05-13_16:32:15.225.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
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-09-23 09:19:56ID requested
12025-05-13 16:32:15announced
Publication List
no publication
Keyword List
submitter keyword: Cellular senescence, Doxorubicin, Ovarian aging, Senescence-Associated Secretory Phenotype (SASP), Data-independent acquisition, Quantitative proteomics, Reproductive aging
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
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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