PXD020343-1

PXD020343 is an original dataset announced via ProteomeXchange.

Title	Specific proteome changes in platelets from individuals with GATA1-, GFI1B- and RUNX1-linked bleeding disorders
Description	Mutations in the transcription factors GATA1, GFI1B and RUNX1 (GATA Binding Factor 1, Growth Factor Independence 1B, Runt-related transcription factor 1) cause familial platelet and bleeding disorders. Mutant platelets exhibit common abnormalities including an α-granule reduction. This suggests that similar pathways are deregulated by different transcription factor mutations. To identify common factors, full platelet proteomes from individuals with mutant GATA1R216Q, GFI1BQ287*, RUNX1TD2-6, or RUNX1Q154Rfs, and healthy controls were examined by label free quantitative mass spectrometry. Unsupervised clustering analysis of 2823 reliably quantified proteins revealed profound differences between cases and controls. Among cases, 82 of 174 significantly downregulated proteins were assigned to platelet function, hemostasis and granule biology, in line with platelet dysfunction and bleedings. Remarkably, only two of these proteins were diminished in all affected cases. This indicates that transcription factor mutations alter platelet proteomes in distinct largely non-overlapping manners. In contrast to the two common diminished proteins, 46 proteins were overrepresented in all affected cases compared to controls. These proteins converged to mitochondrial, metabolic and other biological processes. This work provides the quantitative landscape of proteins that affect platelet function when deregulated by mutated transcription factors in inherited bleeding disorders.
HostingRepository	PRIDE
AnnounceDate	2022-02-22
AnnouncementXML	Submission_2022-02-22_05:04:50.279.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Floris van Alphen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-13 17:43:59	ID requested
⏵ 1	2022-02-22 05:04:50	announced
2	2023-11-14 08:51:20	announced	2023-11-14: Updated project metadata.

10.1182/BLOOD.2020008118;

submitter keyword: Transcription factors, GFI1B, RUNX1, GATA1, platelet disorders, bleeding

Bert A. van der Reijden
contact affiliation	Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands
contact email	bert.vanderreijden@radboudumc.nl
lab head
Floris van Alphen
contact affiliation	Sanquin Research
contact email	F.vanalphen@sanquin.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020343
     1. Label: PRIDE project
     2. Name: Specific proteome changes in platelets from individuals with GATA1-, GFI1B- and RUNX1-linked bleeding disorders