PXD065562-1

PXD065562 is an original dataset announced via ProteomeXchange.

Title	Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity
Description	A deeper understanding of the processes that sustain long-term reprogramming of rapidly turned-over cells in humans can offer unprecedented therapeutic potential, especially for immune cells like neutrophils, given their short lifespan in circulation and importance in both acute and chronic diseases. Hypoxia is a hallmark of a plethora of disease states and significantly shapes neutrophil effector functions. However, its potential contribution to long-term neutrophil reprogramming remains largely unexplored. We have observed persistent perturbations in newly formed circulating neutrophils’ phenotype and function in patients 3-6 months following hospitalisation with acute respiratory distress syndrome (ARDS), where poor oxygenation takes place. These lasting changes are associated with widespread loss of H3K4me3 in genomic regions of relevance to neutrophil activities. Notably, the replication of these findings in healthy volunteers months following altitude induced hypoxaemia attributes a role to the oxygen deprivation as a driver for long-term neutrophil reprogramming. Mechanistically, mouse models of systemic hypoxia reveal deleterious outcomes for infection and show that persistent loss of H3K4me3 originates in proNeu and preNeu populations within the bone marrow and is linked to hypoxia-driven n terminal histone 3 clipping. Thus, we present novel evidence that acute adaptations to systemic hypoxia trigger central changes in newly formed neutrophil populations, resulting in long-term impairment of effector functions and placing hypoxia as a crucial orchestrator of sustained neutrophil reprogramming.
HostingRepository	PRIDE
AnnounceDate	2025-09-22
AnnouncementXML	Submission_2025-09-22_07:08:06.158.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von Kriegsheim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	timsTOF SCP

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-27 07:33:07	ID requested
⏵ 1	2025-09-22 07:08:06	announced

Dataset with its publication pending

submitter keyword: H3K4me3,Neutrophils, Methylation, Immunology

Prof. Alexander von Kriegsheim
contact affiliation	Personal Chair of Cancer Network Biology, Centre for Cancer Research, Institute of Genetics and Cancer, The University of Edinburgh
contact email	Alex.VonKriegsheim@ed.ac.uk
lab head
Alex von Kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ed.ac.uk
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/2025/09/PXD065562

PRIDE project URI

• PRIDE
  1. PXD065562
     1. Label: PRIDE project
     2. Name: Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity