Extended Data Fig. 5: Glucose-derived serine synthesis supports the TCA cycle and αKG-driven differentiation.
From: Extracellular serine controls epidermal stem cell fate and tumour initiation
a, Metabolite pools following 16 h of Ser/Gly starvation (n = 3 biologically independent samples). Data are mean ±SEM. b, Estimation of serine synthesis contribution to αKG pools (n = 6 biologically independent samples, serine uptake data from Fig. 1c) See Methods and Supplementary Tables 2 and 3 for more information. αKGSSP = αKG produced from SSP; SerSSP = serine produced from SSP; SerEC +SG = serine consumed in the presence of extracellular Ser/Gly; SerEC –SG = serine secreted in the absence of extracellular Ser/Gly; GlnIC = available intracellular glutamine pool; GlnEC +SG = glutamine consumed in the presence of extracellular Ser/Gly; GluEC +SG = glutamate secreted in the presence of extracellular Ser/Gly. Data are mean ±SEM. c, Intracellular fumarate and malate in WT EpdSCs expressing indicated hairpins following 16 h Ser/Gly deprivation (n = 3 biologically independent samples). Data are mean ±SEM. d, Involucrin staining in cells supplemented with 1 mM formate, 4 mM DM-αKG or 4 mM DM-succinate (n = 3 independent experiments). Data are mean ±SEM. e, Representative immunoblot for H3K27me3 levels. See Supplementary Table 4 for quantification of immunoblot in triplicate independent experiments. f, Immunofluorescence for H3K27me3 upon culture in low Ser/Gly or Ser/Gly-free medium (n = 3 independent experiments). Data are mean ±SEM. g, Immunofluorescence for H3K27me3 upon culture in serine free, glycine free, or Ser/Gly-free medium (n = 3 independent experiments). Data are mean ±SEM. Statistical significance was determined using a two-way ANOVA with Sidak’s multiple comparison test for panel a, with Tukey’s multiple comparison test for panel d and g, and an ordinary one-way ANOVA with Tukey’s multiple comparison test for panels c and f. Scanned images of unprocessed blots are shown in Source Data Extended Fig. 5. Numerical data are provided in Statistics Source Data Extended Fig. 5.
