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Metabolism regulates muscle stem cell self renewal by connecting the microenvironment and histone acetylation

ABSTRACT: Skeletal muscle contains a resident population of somatic stem cells capable of both self-renewal and differentiation. The signals that regulate this important decision have yet to be fully elucidated. Here we use single cell RNAseq to identify the innate metabolic signature of muscle stem cells. We show that committed muscle progenitor cells exhibit an enrichment of glycolytic and TCA cycle genes and that extracellular monosaccharide availability regulates intracellular citrate levels and global histone acetylation. Muscle stem cells exposed to a reduced (or altered) monosaccharide environment demonstrate reduced global histone acetylation and transcription of myogenic determination factors (including myod1). Importantly, reduced monosaccharide availability was linked directly to increased rates of asymmetric division and muscle stem cell self-renewal. Our results reveal an important role for the extracellular metabolic environment in the decision to undergo self-renewal or myogenic commitment, suggesting local metabolite production may be a therapeutic target to improve muscle regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE117386 | GEO | 2021/07/18

REPOSITORIES: GEO

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Metabolism regulates muscle stem cell self renewal by connecting the microenvironment and histone acetylation

Project description:Skeletal muscle contains a resident population of somatic stem cells capable of both self-renewal and differentiation. The signals that regulate this important decision have yet to be fully elucidated. Here we use single cell RNAseq to identify the innate metabolic signature of muscle stem cells. We show that committed muscle progenitor cells exhibit an enrichment of glycolytic and TCA cycle genes and that extracellular monosaccharide availability regulates intracellular citrate levels and global histone acetylation. Muscle stem cells exposed to a reduced (or altered) monosaccharide environment demonstrate reduced global histone acetylation and transcription of myogenic determination factors (including myod1). Importantly, reduced monosaccharide availability was linked directly to increased rates of asymmetric division and muscle stem cell self-renewal. Our results reveal an important role for the extracellular metabolic environment in the decision to undergo self-renewal or myogenic commitment, suggesting local metabolite production may be a therapeutic target to improve muscle regeneration.

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AML1-ETO induced leukemia stem cell self-renewal depends on Plcg1

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