ArticleCellular and molecular life sciences : CMLS2024
Lactate promotes H3K18 lactylation in human neuroectoderm differentiation.
Article in Cellular and molecular life sciences : CMLS, 2024. 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.
- Asprosin-driven metabolic-epigenetic rewiring attenuates mesenchymal stem cell senescence with therapeutic benefits for infarcted hearts.Journal of advanced research · 2026Article
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness.Experimental & molecular medicine · 2026Review
- H3K18 lactylation-hexokinase 2 positive feedback loop promotes osteogenesis of ASPCs in facial infiltrating lipomatosis.Stem cell research & therapy · 2025Article
- PFKM Promotes the Progression of Gastric Cancer by Up-regulating CNTN1 Expression Through H3K18la Modification.Applied biochemistry and biotechnology · 2025Article
- Article
- Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate-Lactylation Perspective.International journal of molecular sciences · 2025Review
- Lactylation: a novel driver of drug resistance in the tumor microenvironment.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Harnessing glycolysis in gastric cancer: molecular targets, therapeutic strategies, and clinical horizons.Frontiers in immunology · 2025Review
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Authors and funding
5 authors.
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Abstract
In mammals, early embryonic gastrulation process is high energy demanding. Previous studies showed that, unlike endoderm and mesoderm cells, neuroectoderm differentiated from human embryonic stem cells relied on aerobic glycolysis as the major energy metabolic process, which generates lactate as the final product. Here we explored the function of intracellular lactate during neuroectoderm differentiation. Our results revealed that the intracellular lactate level was elevated in neuroectoderm and exogenous lactate could further promote hESCs differentiation towards neuroectoderm. Changing intracellular lactate levels by sodium lactate or LDHA inhibitors had no obvious effect on BMP or WNT/β-catenin signaling during neuroectoderm differentiation. Notably, histone lactylation, especially H3K18 lactylation was significant upregulated during this process. We further performed CUT&Tag experiments and the results showed that H3K18la is highly enriched at gene promoter regions. By analyzing data from CUT&Tag and RNA-seq experiments, we further identified that four genes, including PAX6, were transcriptionally upregulated by lactate during neuroectoderm differentiation. A H3K18la modification site at PAX6 promoter was verified and exogenous lactate could also rescue the level of PAX6 after shPAX6 inhibition.
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