PXD040865-1

PXD040865 is an original dataset announced via ProteomeXchange.

Title	Ceramide-dependent vesicle secretion modulates the integrated stress response in hematopoietic stem cells
Description	Cellular crosstalk within the bone marrow niche maintains hematopoietic stem and progenitor cell (HSPC) integrity and safeguards lifelong blood and immune cell production. Deeper understanding of reciprocal niche signals governing crucial properties of HSPCs is relevant to the pathophysiology of blood disorders and improving HSPC transplantation. Extracellular vesicles (EVs) are key factors of the HSPC secretome, providing signals that regulate homeostasis and stemness. Here we demonstrate ex vivo blockade of ceramide-dependent vesicle secretion from HSPCs activates an integrated stress response (ISR), promoting downstream mTOR inhibition and metabolic quiescence. Crucially, ceramide-EV depletion leads to striking improvements in long-term transplantation. The aggregate findings link ceramide-dependent EV secretion and the ISR as a regulatory dyad guarding HSPC homeostasis and long-term fitness. Translationally, these data support exploration of ceramide inhibition during ex vivo maintenance of HSPCs for adoptive transfer.
HostingRepository	PRIDE
AnnounceDate	2024-11-12
AnnouncementXML	Submission_2024-11-12_07:17:54.135.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-14 10:02:16	ID requested
⏵ 1	2024-11-12 07:17:55	announced

Hurwitz SN, Jung SK, Kobulsky DR, Fazelinia H, Spruce LA, P, é, rez EB, Groen N, Mesaros C, Kurre P, Neutral sphingomyelinase blockade enhances hematopoietic stem cell fitness through an integrated stress response. Blood, 142(20):1708-1723(2023) [pubmed]

10.1182/blood.2023022147;

submitter keyword: ATF4, exosomes, transplantation, reactive oxygen species, GW4869, hematopoiesis,Hematopoietic stem cells

Peter Kurre, MD
contact affiliation	Children’s Hospital of Philadelphia 3615 Civic Center Blvd. Philadelphia, PA 19104
contact email	kurrep@chop.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
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/2024/11/PXD040865

PRIDE project URI

• PRIDE
  1. PXD040865
     1. Label: PRIDE project
     2. Name: Ceramide-dependent vesicle secretion modulates the integrated stress response in hematopoietic stem cells