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PXD032352

PXD032352 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic Analysis of the IPF Mesenchymal Progenitor Cell Nuclear Proteome Identifies Abnormalities in Key Nodal Proteins That Underlie Their Fibrogenic Phenotype
DescriptionIPF is a progressive fibrotic lung disease whose pathogenesis remains incompletely understood. We have previously discovered pathologic mesenchymal progenitor cells (MPCs) in the lungs of IPF patients. IPF MPCs display a distinct transcriptome and create sustained interstitial fibrosis in immune deficient mice. However, the precise pathologic alterations responsible for this fibrotic phenotype remain to be uncovered. Quantitative mass spectrometry and interactomics is a powerful tool that can define protein alterations in specific subcellular compartments that can be implemented to understand disease pathogenesis. We employed quantitative mass spectrometry and interactomics to define protein alterations in the nuclear compartment of IPF MPCs. We identified increased nuclear levels of PARP1, CDK1, and BACH1. Interactomics implicated PARP1, CDK1, and BACH1 as key hub proteins in the DNA damage/repair, differentiation, and apoptosis signaling pathways respectively. Loss of function and inhibitor studies demonstrated important roles for PARP1 in DNA damage/repair, CDK1 in regulating IPF MPC stemness and self-renewal, and BACH1 in regulating IPF MPC viability. Quantitative mass spectrometry combined with interactomics is a powerful tool for defining alterations in key proteins important in uncovering disease mechanisms.
HostingRepositoryPRIDE
AnnounceDate2022-08-12
AnnouncementXMLSubmission_2022-08-12_00:17:07.728.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAdam Gilbertsen
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-17 04:12:38ID requested
12022-08-12 00:17:08announced
Publication List
Yang L, Yang J, Jacobson B, Gilbertsen A, Smith K, Higgins L, Guerrero C, Xia H, Henke CA, Lin J, Regulation of CD44 v6 Expression. Front Oncol, 12():862250(2022) [pubmed]
Keyword List
submitter keyword: Idiopathic pulmonary fibrosis (IPF), mesenchymal progenitor cells (MPCs), nuclear fraction, quantitative mass spectrometry, Ingenuity pathway analysis, DNA damage, differentiation, apoptosis
Contact List
Craig Henke
contact affiliation1Department of Medicine, University of Minnesota, 420 Delaware Street, SE, Minneapolis, Minnesota 55455, USA
contact emailhenke002@umn.edu
lab head
Adam Gilbertsen
contact affiliationUniversity of Minnesota
contact emailgilbe398@umn.edu
dataset submitter
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Dataset FTP location
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