PXD006054

PXD006054 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial respiratory chain is essential for hematopoietic stem cell function
Description	Adult and fetal hematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anemia and prenatal death. RISP null fetal HSCs displayed impaired respiration resulting in a decreased NAD+/NADH ratio. RISP null fetal HSCs and progenitors exhibited an increase in both DNA and histone methylation concomitant with increases in 2-hydroxyglutarate (2-HG), a metabolite known to inhibit DNA and histone demethylases. RISP inactivation in adult HSCs also impaired respiration resulting in loss of quiescence resulting in severe pancytopenia and lethality. Thus, respiration is dispensable for adult or fetal HSC proliferation, but essential for fetal HSC differentiation and maintenance of adult HSC quiescence.
HostingRepository	PRIDE
AnnounceDate	2017-09-13
AnnouncementXML	Submission_2017-09-13_04:46:07.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jacek Sikora
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monomethylated residue; trimethylated residue; acetylated residue; dimethylated residue
Instrument	TSQ Quantum Ultra

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-08 06:05:10	ID requested
⏵ 1	2017-09-13 04:46:08	announced

Ans, ó E, Weinberg SE, Diebold LP, Thompson BJ, Malinge S, Schumacker PT, Liu X, Zhang Y, Shao Z, Steadman M, Marsh KM, Xu J, Crispino JD, Chandel NS, The mitochondrial respiratory chain is essential for haematopoietic stem cell function. Nat Cell Biol, 19(6):614-625(2017) [pubmed]

curator keyword: Biological

submitter keyword: Mitochondria, Metabolism, Stem Cell, HSC, Histone Modifications

Neil L. Kelleher
contact affiliation	Chemistry of Life Processes Institute, Proteomic Center of Excelence, Northwestern University, USA
contact email	n-kelleher@northwestern.edu
lab head
Jacek Sikora
contact affiliation	National Resource for Translational and Developmental Proteomics, Proteomics Center of Excellence, Northwestern University
contact email	j.sikora@northwestern.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/2017/09/PXD006054

PRIDE project URI

• PRIDE
  1. PXD006054
     1. Label: PRIDE project
     2. Name: Mitochondrial respiratory chain is essential for hematopoietic stem cell function