Ductal or Ngn3+ cells do not contribute to adult pancreatic islet beta-cell neogenesis in homeostasis
The adult pancreatic ducts have long been proposed to contain rare progenitors, some of which expressing Ngn3, that generate new beta cells in endocrine-islet homeostasis. Due to their postulated rarity and the lack of definitive markers, the existence or absence of ductal endocrine progenitors remains unsettled despite many studies. Genetic lineage tracing of ductal cells or Ngn3<sup>+</sup> cells with currently available CreER drivers has been complicated by off-target labeling of pre-existing beta cells. Here, using dual-recombinase-mediated intersectional genetic strategy and newly-derived Ngn3-2A-CreER and Hnf1b-2A-CreER knock-in drivers, we succeeded in specifically labeling Ngn3-positive cells and Hnf1b-positive ductal cells without marking pre-existing beta cells. These data revealed no evidence of de novo generation of insulin-producing beta cells from ductal cells or endogenous Ngn3-positive cells in the adult pancreas during homeostasis.
Authors
- Hui Chen (ORCID: https://orcid.org/0009-0005-5767-0501)
- Huan Zhao (ORCID: https://orcid.org/0000-0001-6319-949X)
- Xiuzhen Huang (ORCID: https://orcid.org/0000-0002-4087-8964)
- Zixin Liu (ORCID: https://orcid.org/0000-0002-1085-8911)
- Qiao Zhou (ORCID: https://orcid.org/0000-0002-0099-3909)
- Maoying Han (ORCID: https://orcid.org/0000-0003-3532-4921)
- Zan Lv (ORCID: https://orcid.org/0000-0001-9743-4419)
- Kuo Liu (ORCID: https://orcid.org/0000-0003-0757-7833)
- Bin Zhou (ORCID: https://orcid.org/0000-0001-5278-5522)
- Jie Lu (ORCID: https://orcid.org/0000-0002-1814-2125)
- Ximeng Han (ORCID: https://orcid.org/0000-0002-1081-7052)
- Xiuxiu Liu (ORCID: https://orcid.org/0000-0002-3807-5417)
Institutions
- Shanghai Jiao Tong University (CN)
- Cornell University (US)
- ShanghaiTech University (CN)
- Center for Excellence in Molecular Cell Science (CN)
- Regenerative Medicine Institute (MX)
- Shanghai First People's Hospital (CN)
- Institute for Advanced Study (DE)
Publication Details
- Journal
- The EMBO Journal
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1038/s44318-025-00434-z
- Citations
- 2
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 4.01
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China