Fig. 6: Lactate increases TCF-1 expression through inhibition of histone deacetylases (HDAC).

a Potential mechanisms for lactate induced TCF-1 upregulation. b Heatmap of significantly changed metabolites in CD8⁺ T cells treated with or without 40 mM lactate. c Source of upregulated metabolites with 40 mM lactate treatment. d TCF-1 protein expression in CD8⁺ T cells treated by different metabolites, GPCR agonist or HDAC inhibitors (n = 3 biologically independent samples). e Gene expression of Tcf7 in CD8⁺ T cells treated by different metabolites, GPCR agonist or HDAC inhibitors. The concentration of different metabolites was the same as the highest concentration in d (n = 6 biologically independent samples). f Western blot of histone H3K27ac of CD8⁺ T cells cultured with or without 40 mM lactate (One representative data was shown from 3 independently repeated experiments). g Quantification of H3K27ac enrichment by CUT&RUN PCR at the Tcf7 super enhancer locus (n = 3 biologically independent samples). Data are shown as means ± SEM. P-value was determined by two-tail unpaired t-test without adjustment (d, e) or two-tail ratio paired t-test (g). Source data are provided in Source Data file.