Fig. 5: Human PDA tumors exhibit differential ISR activation.
a, Immunostaining for ASNS in human PDA tissues; dashed boxes are magnified in insets; scale bars, 100 µm. b, UMAP representations of KRT19 expression delineating the epithelial cell population identified from single-cell RNA analysis of a tumor biopsy of PDA individual 1229. c, UMAP representation of the three cell clusters within the epithelial population in b. d, Non-hierarchical clustering analysis of epithelial clusters across a set of ISR genes. e, Immunoblotting analysis of c-Myc, ATF4, ASNS and vinculin of clonal cells lines derived from the PATC53 human PDA tumor model; red, ISR low; blue, ISR high; purple, does not fit either category. The image is representative of three individual experiments. f, Dose–response of PATC53 clones to oligomycin; blue, insensitive clones; red, sensitive clones; n = 3 biological replicates per clone. g, Clonal line PATC53-23 was encoded with a fluorescent label and plated in direct coculture with unlabeled clones PATC53-23 or PATC53-34. h, Cell numbers of labeled PATC53-23 cocultures treated with 0.5 nM oligomycin or 125 µM phenformin relative to vehicle control (n = 3 biological replicates). Error bars are representative of mean ± s.d.; *P ≤ 0.05 and ***P ≤ 0.001 by two-tailed Student’s t-test; oligomycin P = 0.012 and phenformin P = 0.0002 (h).
