PXD032352

PXD032352 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-17 04:12:38	ID requested
⏵ 1	2022-08-12 00:17:08	announced

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]

submitter keyword: Idiopathic pulmonary fibrosis (IPF), mesenchymal progenitor cells (MPCs), nuclear fraction, quantitative mass spectrometry, Ingenuity pathway analysis, DNA damage, differentiation, apoptosis

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

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PRIDE project URI

• PRIDE
  1. PXD032352
     1. Label: PRIDE project
     2. Name: Proteomic Analysis of the IPF Mesenchymal Progenitor Cell Nuclear Proteome Identifies Abnormalities in Key Nodal Proteins That Underlie Their Fibrogenic Phenotype