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. 2025 Apr 9;44(10):2856–2881. doi: 10.1038/s44318-025-00434-z

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© The Author(s) 2025

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.

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Figure EV4 — (A) Immunostaining for tdT, Ins, Gcg, Sst, and PP on pancreatic sections of Ins2-DreER;R26-R-tdT-DTR with PBS or DT treatment. (B) Immunostaining for tdT, Gcg, Sst, PP and E-cad on pancreatic sections of Ins2-DreER;R26-R-tdT-DTR with PBS or DT treatment. (C) Schematic showing the experimental strategy of Ins2-DreER;Ngn3-2A-CreER;NR1;R26-R-tdT-DTR. (D) Immunostaining for tdT, zsGreen and CK19 on pancreatic sections of Ins2-DreER;Ngn3-2A-CreER;NR1;R26-R-tdT-DTR mice with PBS or DT treatment. (E) Quantification of zsGreen⁺ ductal cells per section of Ins2-DreER;Ngn3-2A-CreER;NR1;R26-R-tdT-DTR mice with PBS or DT treatment. Data are mean ± SD; PBS, n = 4 biological replicates; DT, n = 4 biological replicates; P = 0.68; n.s., non-significant. In each sample, islets from 10 pancreas sections were quantified. Two-tailed unpaired Student’s t-tests were used for statistical comparisons and p < 0.05 was accepted as statistically significant. (F) Schematic showing the experimental strategy. (G) H.E. image of unligated head and ligated tail of the pancreas from Ins2-DreER;Ngn3-CreER;NR1 mice 2 weeks after pancreatic ductal ligation (PDL) injury. (H) Immunostaining for tdT, zsGreen and Insulin on sections of unligated head of the pancreas from Ins2-DreER;Ngn3-CreER;NR1 mice. (I) Immunostaining for tdT, zsGreen and Insulin on sections of ligated tail of the pancreas from Ins2-DreER;Ngn3-CreER;NR1 mice. (J) Quantification of the percentages of ZsGreen⁺ cells in Ins⁺ pancreatic beta cells of unligated head and ligated tail of the pancreas from Ins2-DreER;Ngn3-CreER;NR1 mice. Data are mean ± SD; n = 5 biological replicates. In each sample, islets from 10 pancreas sections were quantified. (K) Schematic showing the experimental strategy. (L) H.E. image of unligated head and ligated tail of the pancreas from Ins2-DreER;Ngn3-2A-CreER;NR1 mice 2 weeks after PDL injury. (M) Immunostaining for tdT, zsGreen and Insulin on sections of unligated head of the pancreas from Ins2-DreER;Ngn3-2A-CreER;NR1 mice. (N) Immunostaining for tdT, zsGreen and Insulin on sections of ligated tail of the pancreas from Ins2-DreER;Ngn3-2A-CreER;NR1 mice. (O) Quantification of the percentages of ZsGreen⁺ cells in Ins⁺ pancreatic beta cells of unligated head and ligated tail of the pancreas from Ins2-DreER;Ngn3-2A-CreER;NR1 mice. Data are mean ± SD; n = 5 biological replicates. In each sample, islets from 10 pancreas sections were quantified. Scale bars, 100 μm. Each image is representative of 4–5 individual mouse samples.