Extended Data Fig. 8: Additional description of and analyses in KC;Me1^+/+ and KC;Me1^flox/flox mice.

a. Mice with Me1^flox/flox alleles were bred into the KC (LSL-Kras^G12D; Ptf1a^Cre) line. Cre was always maintained in female breeders. Experiments used both male and female mice that were homozygous for the Me1^flox/flox allele and mice that were Me1^+/+ (wildtype). b. Immunostaining for ME1 in 16-week-old KC;Me1^+/+ and KC;Me1^flox/flox pancreas. Scale bar = 50μm. c. Hematoxylin & eosin (H&E) staining and immunostaining for amylase (AMY; acinar cells), cytokeratin 19 (CK19; ductal, metaplastic, neoplastic cells), and Ki67 (proliferation) in pancreas of 8-week-old KC;Me1^+/+ and KC;Me1^flox/flox mice. Scale bar = 50μm. d. Percent of Amylase+ area in pancreas as quantified from male (closed circle) and female (open circle) mice in KC;Me1^+/+ (grey bar) and KC;Me1^flox/flox (blue bar) mice at 8 weeks. n = 4 mice for each genotype. Bars represent the mean with standard deviation. P-values were calculated using a Student’s t-test (unpaired, two-tailed). e. Percent of CK19+ cells and f. Ki67+ cells in the pancreas as quantified from male (closed circle) and female (open circle) KC;Me1^+/+ (grey bar) and KC;Me1^flox/flox (blue bar) mice at 8 weeks. In CK19 plot: n = 5 KC;Me1^+/+ and n = 6 KC;Me1^flox/flox mice. In Ki67 plot: n = 6 mice for each genotype. Bars represent the mean with standard deviation. P-values were calculated using a Student’s t-test (unpaired, two-tailed). g. Immunostaining for Amylase (AMY), in 8-week and 16-week-old KC;Me1^+/+ and KC;Me1^flox/flox pancreas. Alcian blue (PanIN-produced mucin) & nuclear fast red counterstain in pancreas of 26-week- KC;Me1^+/+ and KC;Me1^flox/flox mice. Scale bar = 500μm. h. Pancreas weight (PW) to body weight (BW) ratios in 8-, 16-, and 26-week-old KC;Me1^+/+ and KC;Me1^flox/flox mice. Bars represent the mean with standard deviation. Ratios are not significantly different as calculated using a Student’s t-test (unpaired, two-tailed) for each age. Sample sizes for each age are as follows: 8 week, n = 6 KC;Me1^+/+ and n = 8 KC;Me1^flox/flox; 16 week, n = 6 KC;Me1^+/+ and n = 8 KC;Me1^flox/flox; 26 week, n = 5 KC;Me1^+/+ and n = 7 KC;Me1^flox/flox. i. Pathological grading of 26-week-old KC;Me1^+/+ and KC;Me1^flox/flox pancreas tissues representing the % of total tissue area with acinar cells, ADM, and PanIN lesions. n = 4 mice per genotype. Bars represent the mean with standard deviation. P-values were calculated using a two-way ANOVA with Tukey’s multiple comparisons test. j. Pathological grading of 1-year-old KC;Me1^+/+ pancreas tissues representing the % of total tissue area with acinar cells, ADM, and PanIN lesions. n = 4 mice. Bars represent the mean with standard deviation.

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