PXD032352 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomic Analysis of the IPF Mesenchymal Progenitor Cell Nuclear Proteome Identifies Abnormalities in Key Nodal Proteins That Underlie Their Fibrogenic Phenotype |
Description | IPF 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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-08-12 |
AnnouncementXML | Submission_2022-08-12_00:17:07.728.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Adam Gilbertsen |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-03-17 04:12:38 | ID requested | |
⏵ 1 | 2022-08-12 00:17:08 | announced | |
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 affiliation | 1Department of Medicine, University of Minnesota, 420 Delaware Street, SE, Minneapolis, Minnesota 55455, USA |
contact email | henke002@umn.edu |
lab head | |
Adam Gilbertsen |
contact affiliation | University of Minnesota |
contact email | gilbe398@umn.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD032352
- Label: PRIDE project
- Name: Proteomic Analysis of the IPF Mesenchymal Progenitor Cell Nuclear Proteome Identifies Abnormalities in Key Nodal Proteins That Underlie Their Fibrogenic Phenotype