Mitochondrial respiratory chain is essential for hematopoietic stem cell function

ABSTRACT: 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.

OTHER RELATED OMICS DATASETS IN: PRJNA376700

INSTRUMENT(S): TSQ Quantum Ultra

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver, Hematopoietic Stem Cell

SUBMITTER: Jacek Sikora  

LAB HEAD: Neil L. Kelleher

PROVIDER: PXD006054 | Pride | 2017-09-13

REPOSITORIES: Pride