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. 2018 Sep 12;8:13713. doi: 10.1038/s41598-018-32054-5

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Increased acinar cell apoptosis and proliferation in HIF2α-overexpressing pancreata. (A,B) TUNEL staining shows an increase in apoptotic acinar cells in the pancreas of two-week-old Pdx1-Cre;HIF2dPA mice (B, white arrowheads) compared with wild-type (A) mice. (C) Quantification of apoptotic cells measured as TUNEL positive-cells per total number of amylase-positive cells. Individual data points are presented. The mean value is indicated as a horizontal line. (D,E) Immunohistochemistry for cleaved caspase-3 confirms the increase in apoptotic cells in Pdx1-Cre;HIF2dPA pancreata (E, black arrowheads) compared to control pancreata (D). Increased acinar cell proliferation in two-week-old Pdx1-Cre;HIF2dPA pancreata (G) compared to control pancreata (F), as shown by double amylase/Ki-67 immunofluorescence. Increased ductal cell proliferation in two-week-old Pdx1-Cre;HIF2dPA pancreata (I) compared to control pancreata (H), as shown by double KRT19/Ki-67 immunofluorescence. (J) Quantification of acinar (left graph) and ductal (right graph) proliferating cells, measured as the average number of Ki67-positive cells per amylase- or KRT19-positive cells. Data points represent values for each individual mouse. The mean value is indicated as a horizontal line. Scale bars = 50 µm for A,B,D and E; 100 µm for F–I. **P < 0.01; ***P < 0.001.