Fig. 3: Me1 loss accelerates the formation of early precursor lesions and PDAC progression.
From: NADPH-producing enzymes restrict the formation of pancreatic precancerous lesions
a, Schematic of malic enzyme 1 (ME1) function and related metabolic pathways. ME1 is a cytosolic enzyme that converts malate to pyruvate, generating NADPH in the process. Malate can come from the cytosol or be transported across the mitochondrial membrane from the TCA cycle. The pyruvate generated by ME1 can enter the TCA cycle. Mitochondria (Mito) presented in pink. b, H&E staining and immunostaining for AMY (acinar cells), CK19 (ductal, metaplastic, neoplastic cells) and Ki67 (proliferation) in pancreas of 16-week-old KC;Me1+/+ and KC;Me1flox/flox mice. Scale bars, 50 μm. c, Percentage of AMY-positive area in pancreas as quantified from male (closed circles) and female (open circles) KC;Me1+/+ and KC;Me1flox/flox mice at 16 weeks; n = 4 mice for each genotype. Bars represent the mean values; error bars, s.d. P values were calculated using a Student’s t-test (unpaired, two-tailed). d,e, Percentage of CK19+ cells (d) and Ki67+ cells (e) in the pancreas as quantified from male (closed circles) and female (open circles) KC;Me1+/+ and KC;Me1flox/flox mice at 16 weeks; n = 6 mice for each genotype. Bars represent the mean values; error bars, s.d. P values were calculated using a Student’s t-test (unpaired, two-tailed). f, H&E staining, Alcian Blue staining (for PanIN-produced mucins) and CK19 (ductal, metaplastic, neoplastic cells) immunostaining in 26-week-old KC;Me1+/+ and KC;Me1flox/flox mice. Scale bars, 100 μm. g, Pathological grading of pancreas tissues from 26-week-old KC;Me1+/+ and KC;Me1flox/flox mice, representing the percentage of total tissue area with acinar cells, ADM and PanIN lesions; n = 4 mice for each genotype. Bars represent the mean values; error bars, s.d. P values were calculated using a two-way ANOVA with Tukey’s post hoc test. h, H&E staining in 1-year-old KC;Me1+/+ and KC;Me1flox/flox mice. Scale bar, 100 μm. i, Pathological grading of pancreas tissues from 1-year-old KC;Me1+/+ and KC;Me1flox/flox mice, representing the percentage of total tissue area with acinar cells and PDAC; n = 4 mice for each genotype. Bars represent the mean values; error bars, s.d. P values were calculated using a two-way ANOVA with Tukey’s post hoc test.
