Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function
Open accessAbstract
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.
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Glucose metabolism is critical for MuSCs and influences histone acetylation.
“Glucose metabolism is critical for MuSCs and influences histone acetylation124.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [124]
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- Authors
- 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.
- Affiliations
- Institute for Stem Cell Biology and Regenerative Medicine (US)
- University of Pennsylvania (US)
- Stanford Medicine (US)
- Corresponding author
- Blau, Helen M.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 27
- Issue
- 13
- Pages
- 3939-3955.e6
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6788807
- OpenAlex
- W2955111823
- Cited by
- 159
- References
- 76
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 29 · 2023: 24 · 2022: 25 · 2021: 22 · 2020: 17 · 2019: 2
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AG020961, R01 NS089533, S10RR027431-01)
- Donald E. and Delia B. Baxter Foundation
- Canadian Institutes of Health Research (F32 GM112425-02)
- California Institute for Regenerative Medicine (RB5-07469)
- National Science Foundation (1309047)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- glucose metabolism, histone acetylation, muscle stem cells, muscle regeneration, pyruvate dehydrogenase, acetyl-CoA, mitochondrial respiration, myogenesis, self-renewal, chromatin accessibility, quiescent stem cells, metabolic reprogramming
- MeSH terms
- Acetylation, Animals, Glucose, Histones, Regeneration, Mass Spectrometry, Muscle, Skeletal, Myoblasts, Skeletal, Mice, Single-Cell Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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