Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function, 2019, Blau et al

Andy

Andy

Retired committee member
Maybe this could be part of our muscle fatiguability?
Highlights
  • Histone acetylation levels change with muscle stem cell states during regeneration
  • Mitochondrial glucose utilization determines overall histone acetylation levels
  • PDH activity controls histone acetylation and myogenic differentiation potential
  • PDK2 and PDK4 are required for skeletal muscle regeneration in vivo
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.
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www.cell.com/cell-reports/fulltext/S2211-1247(19)30731-4
 
Andy said:
Maybe this could be part of our muscle fatiguability?

www.cell.com/cell-reports/fulltext/S2211-1247(19)30731-4
Click to expand...

Nice find Andy. Not sure if you know that Helen Blau is among the top muscle biologists in the world. This work is on muscle stem cells (previously known as satellite cells) in rodents. These stem cells are usually quiescent in adult muscle because muscle fibers are post-mitotic (fully differentiated, do not proliferate). The role of muscle stem cells in humans is not clear except with focal injury.
 
Susan K said:
Nice find Andy. Not sure if you know that Helen Blau is among the top muscle biologists in the world. This work is on muscle stem cells (previously known as satellite cells) in rodents. These stem cells are usually quiescent in adult muscle because muscle fibers are post-mitotic (fully differentiated, do not proliferate). The role of muscle stem cells in humans is not clear except with focal injury.
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Thanks. :)

I'm afraid I'm someone with no biology/medical training of any sort but daily emails that highlight new papers that match certain keywords, and from there I guess what might be useful/interesting. I rely on the members with brains to pick up on anything worthwhile. :)
 
A brief glance suggests that this paper has similarities with Neil McGregor's talk at the EMERGE conference.

I have just read thro' Cort's summary from HR produced on 15 June 2019. It mentions histone acetylation alongside the problems of glycolysis etc.
 
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