Department of Physiology, Centre for Muscle Research, The University of Melbourne, Melbourne, Victoria, Australia.
Curr Opin Clin Nutr Metab Care. 2018 Jul;21(4):240-245. doi: 10.1097/MCO.0000000000000472.
To discuss how innate muscle stem-cell metabolism and nutrient availability can provide temporal regulation of chromatin accessibility and transcription.
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.
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.
讨论先天性肌肉干细胞代谢和营养供应如何提供染色质可及性和转录的时间调节。
荧光激活细胞分选与全转录组测序首次揭示，静止和增殖的骨骼肌干细胞经历代谢重编程过程，从静止时的脂肪酸氧化到增殖时的糖酵解。通过免疫荧光和染色质免疫沉淀测序的结合，这种代谢转变与关键代谢物的可用性变化有关，这些代谢物对于组蛋白（去）乙酰化和（去）甲基化至关重要，包括乙酰辅酶 A、s-腺苷甲硫氨酸和α-酮戊二酸。重要的是，这些代谢物可用性的变化与肌肉干细胞功能有关。
这些结果提供了对肌肉干细胞如何与其局部环境相互作用的更深入了解，对代谢性疾病、骨骼肌再生和细胞移植治疗具有重要意义。
