Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function
| Autor: | Nora Yucel, Glenn J. Markov, Peder J. Lund, Michael Angelo, Helen M. Blau, Yu Xin Wang, Ermelinda Porpiglia, Sean C. Bendall, Thach Mai, Benjamin A. Garcia |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Myoblasts Skeletal Myoblasts Skeletal/metabolism Carbohydrate metabolism Article Mass Spectrometry General Biochemistry Genetics and Molecular Biology Histones Mice 03 medical and health sciences 0302 clinical medicine Animals Regeneration Myocyte Muscle Skeletal lcsh:QH301-705.5 biology Chemistry Acetylation Metabolism Pyruvate dehydrogenase complex Cell biology Chromatin Glucose 030104 developmental biology Histone Muscle Skeletal/cytology lcsh:Biology (General) biology.protein Single-Cell Analysis Stem cell 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 27, Iss 13, Pp 3939-3955.e6 (2019) Yucel, N, Wang, Y X, Mai, T, Porpiglia, E, Lund, P J, Markov, G, Garcia, B A, Bendall, S C, Angelo, M & Blau, H M 2019, ' Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function ', Cell Reports, vol. 27, no. 13, pp. 3939-3955.e6 . https://doi.org/10.1016/j.celrep.2019.05.092 Cell reports |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.05.092 |
| Popis: | SUMMARY The impact of glucose metabolism on muscle regeneration remains unresolved. We identify glucose metabolism as a crucial driver of histone acetylation and myogenic cell fate. We use single-cell mass cytometry (CyTOF) and flow cytometry to characterize the histone acetylation and metabolic states of quiescent, activated, and differentiating muscle stem cells (MuSCs). We find glucose is dispensable for mitochondrial respiration in proliferating MuSCs, so that glucose becomes available for maintaining high histone acetylation via acetyl-CoA. Conversely, quiescent and differentiating MuSCs increase glucose utilization for respiration and have consequently reduced acetylation. Pyruvate dehydrogenase (PDH) activity serves as a rheostat for histone acetylation and must be controlled for muscle regeneration. Increased PDH activity in proliferation increases histone acetylation and chromatin accessibility at genes that must be silenced for differentiation to proceed, and thus promotes self-renewal. These results highlight metabolism as a determinant of MuSC histone acetylation, fate, and function during muscle regeneration. Graphical Abstract In Brief Yucel et al. identify a link between stem cells’ metabolism and their fate and function. Mitochondrial glucose utilization determines remodeling of the histone acetylation landscape of muscle stem cells during tissue regeneration. Pyruvate dehydrogenase (PDH) is a pivotal control point for this and determines the differentiation potential of myogenic progenitors. |
| Databáze: | OpenAIRE |
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