Fig 2. The ectopic expression of Neurog3 triggered in adult pancreatic ductal cells results in hyperplastic islets with remodeled endocrine cell distribution but unchanged relative ratios.

(A-B) Mosaic photographs of pancreatic sections of control (A) and HNFN3OE animal treated with Tam for 12 months (B) and assayed for insulin expression using immunohistochemical detection. Note the increase in islet number and size in Tam-treated HNFN3OE animal (B) compared to vehicle-administered control (A). Control in A is age-matched with B. (C) HNFOE littermates were treated with Tamoxifen for the indicated duration at the specified starting ages. The islets size and number were then analyzed for each group and compared to age-matched controls. Note the progressive islet hypertrophy and increase in islet count, these depending on the duration of Tam administration. The ratio displayed in the table indicate the relative increase in islet surface and count ± SEM, n = 3 per group. (D-E) Immunostaining of islets of Langerhans from vehicle- (D) and Tam- (E) treated pancreata displaying the distribution of insulin-, glucagon- and somatostatin-expressing cells. The typical islet organization observed in controls, with a core of β-cells surrounded by non β-cells (D), appears altered in Tam-treated animals (E), with a preferential localization of α- and δ-cells at one pole of the islets, in proximity of ducts (E, S1 Movie). For clarity, the ductal lumen is outlined with yellow lines. (F) Relative distribution of the insulin-, glucagon-, and somatostatin-producing cell populations in Tam-treated HNFN3OE pancreata compared to controls (Controls n = 6, 1m n = 4, 3m n = 3, 12m n = 3). Interestingly, the increases in insulin-, glucagon-, and somatostatin-producing cell counts are found to be similar in Tam-treated HNFN3OE animals, their relative proportions remaining unchanged when compared to controls. Statistics were performed using the Mann-Whitney test or unpaired t-test with Welch’s correction.