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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 EV2 — (A) Schematic showing the labeling strategy of Ins2-DreER;R26-TLR. (B) Schematic showing the experimental strategy of Ins2-DreER;R26-TLR with tamoxifen (Tam) treatment. (C) Whole-mount fluorescent images of pancreas from Ins2-DreER;R26-TLR. Arrowheads, zsGreen⁺ islets. (D) Immunostaining for ZsGreen, tdT and Ins on pancreatic sections of Ins2-DreER;R26-TLR with Tam treatment. Arrowheads, zsGreen⁺ beta cells. (E) Immunostaining for ZsGreen and Ins on serial sections of one pancreatic islet from Ins2-DreER;R26-TLR with Tam treatment. (F) Quantification of the percentages of ZsGreen⁺tdT^– or tdT⁺ZsGreen^– or ZsGreen⁺tdT⁺ cells in Ins⁺ pancreatic beta cells of Ins2-DreER;R26-TLR. Data are mean ± SD; n = 5 biological replicates. In each sample, islets from 10 pancreas sections were quantified. (G) Schematic showing the experimental strategy of Ins2-DreER;Ngn3-CreER;R26-TLR with oil treatment. (H) Whole-mount fluorescent images of pancreas from Ins2-DreER;Ngn3-CreER;R26-TLR after oil treatment. (I) Immunostaining for ZsGreen, tdT and Ins on pancreatic sections of Ins2-DreER;Ngn3-CreER;R26-TLR after oil treatment. (J) Quantification of the percentage of ZsGreen⁺tdT^– or tdT⁺ZsGreen^– or ZsGreen⁺tdT⁺ cells in Ins⁺ pancreatic beta cells of Ins2-DreER;Ngn3-CreER;R26-TLR after oil treatment. Data are mean ± SD; n = 5 biological replicates. In each sample, islets from 10 pancreas sections were quantified. (K) Schematic showing the experimental strategy of Ins2-DreER;Ngn3-2A-CreER;R26-TLR with oil treatment. (L) Whole-mount fluorescent images of pancreas from Ins2-DreER;Ngn3-2A-CreER;R26-TLR after oil treatment. (M) Immunostaining for ZsGreen, tdT and Ins on pancreatic sections of Ins2-DreER;Ngn3-2A-CreER;R26-TLR after oil treatment. (N) Quantification of the percentage of ZsGreen⁺ or tdT⁺ or ZsGreen⁺tdT⁺ cells in Ins⁺ pancreatic beta cells of Ins2-DreER;Ngn3-2A-CreER;R26-TLR after oil treatment. Data are mean ± SD; n = 5 biological replicates. In each sample, islets from 10 pancreas sections were quantified. Scale bars, yellow, 1 mm; white, 100 μm. Each image is representative of 5 individual samples.