ArticleStem cell research & therapy2025
Extracellular lactate improves neurogenesis by modulating H3K9 lactylation and SnoN expression under hypoxic conditions.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Roles of lactate and protein lactylation in neurogenesis and neurodegenerative disease.Journal of translational medicine · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- A Novel Approach to Neuropathic Pain Treatment: Lactylation Targeting Microglia.Molecular neurobiology · 2026Review
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- Dual roles of lactate and lactylation modification in the nervous system: neuroprotection and neuroinjury.Frontiers in aging neuroscience · 2026Review
- Protein lactylation in Alzheimer's disease: bridging metabolism, pathology, and therapeutic opportunity.Frontiers in aging neuroscience · 2026Review
- Lactylation at the crossroads of metabolism and epigenetics in neuroinflammation.Frontiers in immunology · 2026Review
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
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Authors and funding
10 authors.
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Abstract
backgroundLactate has a beneficial effect on adult neurogenesis and has been identified as a mediator of lactylation of proteins. However, the regulatory role and function of histone lactylation in neurogenesis remain poorly understood. This study aimed to elucidate the relationship between lactate and the fate of neural stem cells (NSCs), and explore the role of histone lactylation in neurogenesis.
methodsUnder hypoxic conditions, NSCs were treated with lactate to investigate its effects on cell fate. Western blot and immunofluorescence staining were performed to detect histone lactylation modifications. RNA-sequencing (RNA-seq) was used to characterize the transcriptome after lactate treatment, in conjunction with Chromatin immunoprecipitation sequencing (ChIP-seq), to identify potential target genes for histone lactylation.
resultsUnder hypoxic conditions, L-lactate promotes neurogenesis and induces H3K9 histone lactylation (H3K9la). The inhibition of L-lactate uptake or production hinders neuronal development and is accompanied by decreased H3K9la. And the inhibition of H3K9la inhibits the differentiation of NSCs into neurons. Furthermore, H3K9la was enriched in the SnoN (also known as Skil) promoter region, and siRNA targeting SnoN inhibits the generation of Doublecortin (DCX)
conclusionL-lactate promotes neurogenesis through H3K9la/SnoN axis under hypoxic environments and SnoN potentially serves as a novel target for enhancing neurological recovery in cerebral ischemia.
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