James G Ryall1, Gordon S Lynch. 1. Department of Physiology, Centre for Muscle Research, The University of Melbourne, Melbourne, Victoria, Australia.
Abstract
PURPOSE OF REVIEW: To discuss how innate muscle stem-cell metabolism and nutrient availability can provide temporal regulation of chromatin accessibility and transcription. RECENT FINDINGS: Fluorescence-activated cell sorting coupled with whole transcriptome sequencing revealed for the first time that quiescent and proliferating skeletal muscle stem cells exhibit a process of metabolic reprogramming, from fatty-acid oxidation during quiescence to glycolysis during proliferation. Using a combination of immunofluorescence and chromatin immunoprecipitation sequencing, this shift in metabolism has been linked to altered availability of key metabolites essential for histone (de)acetylation and (de)methylation, including acetyl-CoA, s-adenosylmethionine and α-ketoglutarate. Importantly, these changes in metabolite availability have been linked to muscle stem-cell function. SUMMARY: Together, these results provide greater insight into how muscle stem cells interact with their local environment, with important implications for metabolic diseases, skeletal muscle regeneration and cell-transplantation therapies.
PURPOSE OF REVIEW: To discuss how innate muscle stem-cell metabolism and nutrient availability can provide temporal regulation of chromatin accessibility and transcription. RECENT FINDINGS: Fluorescence-activated cell sorting coupled with whole transcriptome sequencing revealed for the first time that quiescent and proliferating skeletal muscle stem cells exhibit a process of metabolic reprogramming, from fatty-acid oxidation during quiescence to glycolysis during proliferation. Using a combination of immunofluorescence and chromatin immunoprecipitation sequencing, this shift in metabolism has been linked to altered availability of key metabolites essential for histone (de)acetylation and (de)methylation, including acetyl-CoA, s-adenosylmethionine and α-ketoglutarate. Importantly, these changes in metabolite availability have been linked to muscle stem-cell function. SUMMARY: Together, these results provide greater insight into how muscle stem cells interact with their local environment, with important implications for metabolic diseases, skeletal muscle regeneration and cell-transplantation therapies.