PXD017784

PXD017784 is an original dataset announced via ProteomeXchange.

Title	Neutrophil specific granule and NETosis defect in Gray Platelet Syndrome
Description	Gray Platelet Syndrome (GPS) is an autosomal recessive bleeding disorder characterized by a lack of α-granules in platelets and progressive myelofibrosis. Rare loss of function variants in NBEAL2, a member of the family of BEACH genes, are causal of GPS. The gene is involved in fusion, fission and trafficking of vesicles and granules. Whether NBEAL2 controls the ontogeny of granules of myeloid cells remains disputed. We found that neutrophils obtained from the peripheral blood from GPS patients have a normal distribution of azurophilic granules, but show a deficiency of specific granules, as confirmed by immuno-electron microscopy and mass spectrometry proteomics analyses. In cultures from peripheral CD34+ hematopoietic stem cells (HSCs) into mature neutrophils, the time dynamics showed concordance of NBEAL2 and specific granule protein expression at transcriptional and protein level, which were discordant in neutrophils obtained GPS-HSCs. This is indicative of normal granulopoiesis in GPS and identifies NBEAL2 as an important regulator of granule release (similar to platelets) which is suggested to occur upon egress into the blood stream. Patient neutrophil functions, including production of reactive oxygen species, chemotaxis and killing of bacteria and fungi were intact. Since GPS patients do not excessively suffer from infections, the consequence of the reduced specific granule content and lack of NET formation for innate immunity remains to be explored.
HostingRepository	PRIDE
AnnounceDate	2021-03-04
AnnouncementXML	Submission_2021-03-04_11:38:20.750.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Arie Hoogendijk
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-28 08:04:38	ID requested
⏵ 1	2021-03-04 11:38:21	announced

Aarts CEM, Downes K, Hoogendijk AJ, Sprenkeler EGG, Gazendam RP, Favier R, Favier M, Tool ATJ, van Hamme JL, Kostadima MA, Waller K, Zieger B, van Bergen MGJM, Langemeijer SMC, van der Reijden BA, Janssen H, van den Berg TK, van Bruggen R, Meijer AB, Ouwehand WH, Kuijpers TW, Neutrophil specific granule and NETosis defects in gray platelet syndrome. Blood Adv, 5(2):549-564(2021) [pubmed]

submitter keyword: Neutrophil, Gray platelet syndrome

M. van den Biggelaar
contact affiliation	Laboratory of Proteomics, Department of Molecular Hematology, Sanquin Research, Amsterdam, NL
contact email	m.vandenbiggelaar@sanquin.nl
lab head
Arie Hoogendijk
contact affiliation	Department of Molecular Hematology, Sanquin Research, Amsterdam
contact email	a.hoogendijk@sanquin.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/01/PXD017784

PRIDE project URI

• PRIDE
  1. PXD017784
     1. Label: PRIDE project
     2. Name: Neutrophil specific granule and NETosis defect in Gray Platelet Syndrome