Supplementary Figure 6: Effects of UK-5099 and MPC over expression.

(a) Flux profiling of U-C13 Glucose incorporation into Citrate for tMEF and C2C12 cell lines treated with UK-5099 or Valproic Acid over 4 hours (n = 3 per condition per timepoint). (b) Representative images of infected Lgr5-EGFP (green) organoids with either Empty Vector-mCherry (in red) or MPC1-iRFP (in blue) and MPC2 mCherry (in red). Traces below represent intensity of each color over the length of the line outlined by white dotted line in the image. (n = 4 organoids with at least 15 infected cells per organoid counted). (c) ENCODE track for Myc and associated transcription factors localized to the Mpc1 promoter. (d) Model where crypt homeostasis involves low pyruvate oxidation at the base which increases during differentiation. MPC1 loss leads to reduced pyruvate oxidation, increased glycolysis, increased proliferation, and an expansion of the stem cell compartment within the crypt. Data are mean ± s.e.m. ^∗P < 0.05, ^∗∗P < 0.01, ^∗∗∗P < 0.001. All p values were calculated using Student’s t-test.