Fig. 1: Metabolic characterization reveals two distinct cellular populations from PDA tumors.
a, A polyclonal cell line established from a mouse pancreatic tumor was subcloned into seven clonal lines and subjected to LC–MS/MS metabolomics analysis. b, Heat map representation of significantly different intracellular metabolites pooled from a positive and negative ionization mode analysis among the clonal cell lines grown under the same media conditions; fold change of ±2; P = 0.01 between group 1 clones (E, V and H) and group 2 clones (K, M, N and T). Rows are clonal cell lines in triplicate, and columns represent metabolites (n = 3 biological replicates per cell line). c–f, Sensitivity of clonal cell lines to 33 µM FX11 (c) and IC50 values for aminooxyacetic acid (AOA) (d), oligomycin (e) and phenformin (f); n = 3 biological replicates per cell line. g, Group 1 clones (H and V) and group 2 clones (N and T) were subjected to NAD(P)H FLIM. Data are presented as a ratio of free to protein-bound NAD(P)H; n = 104 clone H cells, n = 108 clone V cells, n = 136 clone N cells and n = 105 clone T cells; OXPHOS, oxidative phosphorylation. h, Histograms of the indicated clones stained with TMRM and analyzed via flow cytometry. i, Ratio of TMRM to MitoTracker Green staining of the indicated clonal lines (n = 2 biological replicates for clone V and n = 3 biological replicates for clones H, N and T). Error bars represent mean ± s.d.; **P ≤ 0.01, ***P ≤ 0.001 and ****P ≤ 0.0001 by two-tailed Mann–Whitney test (c–f and i) or one-way ANOVA with a Tukey post hoc test; P < 0.0001 (c); P < 0.0001 (d); P = 0.0018 (e); P < 0.0001 (f); H versus T P < 0.0001, H versus N P < 0.0001, V versus T P < 0.0001 and V versus N P = 0.0003 (g); P = 0.0043 (i).
