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<p>How it is determined whether postnatal oligodendrocyte progenitor cells (OPCs) will survive, proliferate or differentiate remains unclear. Here we suggest that temporal and brain regional fluctuations of glucose, concomitant with changes in vascularization, modulate OPC population dynamics. We found that regions with high glucose levels exhibited greater OPC proliferation and histone acetylation than regions with low glucose and that this was mediated by the enzyme ATP-citrate lyase (ACLY), which converts glucose-derived citrate to acetyl-CoA. Mice with <i>Acly</i> deletion in OPCs showed a transient hypomyelination phenotype resulting from decreased OPC numbers, whereas their differentiation into oligodendrocytes (OLs) proceeded due to compensatory upregulation of enzymes responsible for extranuclear generation of acetyl-CoA from alternative metabolic substrates. Therefore, OPCs rely on ACLY-dependent nuclear acetyl-CoA from glucose-derived citrate, to regulate proliferation, whereas OLs rely on extranuclear acetyl-CoA from other sources for myelin formation. This suggests a metabolic regulation of OL lineage cell population dynamics.</p>

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Glucose-dependent spatial and temporal modulation of oligodendrocyte progenitor cell proliferation via ACLY-regulated histone acetylation

  • 期刊论文

  • 发表日期：

    2026年4月30日

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  • Sami Sauma,
  • Stephanie Stransky,
  • Ipek Selcen,
  • Simone Sidoli,
  • Rinat Abzalimov,
  • Ye He,
  • Patrizia Casaccia

摘要

How it is determined whether postnatal oligodendrocyte progenitor cells (OPCs) will survive, proliferate or differentiate remains unclear. Here we suggest that temporal and brain regional fluctuations of glucose, concomitant with changes in vascularization, modulate OPC population dynamics. We found that regions with high glucose levels exhibited greater OPC proliferation and histone acetylation than regions with low glucose and that this was mediated by the enzyme ATP-citrate lyase (ACLY), which converts glucose-derived citrate to acetyl-CoA. Mice with Acly deletion in OPCs showed a transient hypomyelination phenotype resulting from decreased OPC numbers, whereas their differentiation into oligodendrocytes (OLs) proceeded due to compensatory upregulation of enzymes responsible for extranuclear generation of acetyl-CoA from alternative metabolic substrates. Therefore, OPCs rely on ACLY-dependent nuclear acetyl-CoA from glucose-derived citrate, to regulate proliferation, whereas OLs rely on extranuclear acetyl-CoA from other sources for myelin formation. This suggests a metabolic regulation of OL lineage cell population dynamics.