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Mitochondrial hetereogeneity in hematopoietic stem cells (HSC)

ABSTRACT: Quiescence is a fundamental property that maintains hematopoietic stem cells (HSCs)’ potency throughout life. Quiescent HSCs are thought to rely on glycolysis for their energy but the overall metabolic properties of HSCs remain incompletely understood. Using combined approaches including single cell RNA-Seq we show that mitochondrial membrane potential (MMP) distinguishes the quiescent from cycling-primed HSCs. We found that primed but not quiescent HSCs relied readily on glycolysis. Notably, in vivo inhibition of glycolysis robustly enhanced the competitive repopulation ability of primed HSCs. We further show that HSC quiescence is maintained by an abundance of large lysosomes. Repression of lysosomal activation led to further enlargement of lysosomes, while repressing mTOR activation and glucose uptake. This also induced increased lysosomal sequestration of mitochondria and enhanced the competitive repopulation ability of primed HSCs by over 90-fold in vivo. These findings show that restraining lysosomal activity is key in preserving HSC quiescence and potency, and may be therapeutically relevant.

ORGANISM(S): Mus musculus

PROVIDER: GSE141457 | GEO | 2020/03/05

REPOSITORIES: GEO

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