A multimodal cross-species comparison of pancreas development
Human pancreas development remains incompletely characterized due to restricted sample access. We investigate whether pigs resemble humans in pancreas development, offering a complementary large-animal model. As pig pancreas organogenesis is unexplored, we first annotate developmental hallmarks throughout its 114-day gestation. Building on this, we construct a pig single-cell multiome pancreas atlas across all trimesters. Cross-species comparisons reveal pigs resemble humans more closely than mice in developmental tempo, epigenetic and transcriptional regulation, and gene regulatory networks. This further extends to progenitor dynamics and endocrine fate acquisition. Transcription factors regulated by NEUROG3, the endocrine master regulator, are over 50% conserved between pig and human, many being validated in human stem cell models. Notably, we uncover that during embryonic development, emerging beta-cell heterogeneity coincides with a species-conserved primed endocrine cell (PEC) population alongside NEUROG3-expressing cells. Overall, our work lays the foundation for comparative investigations and offers unprecedented insights into evolutionarily conserved pancreas organogenesis mechanisms across animal models.
Authors
- Sean de la O (ORCID: https://orcid.org/0000-0001-6607-9610)
- Michael Sterr
- Krzysztof Flisikowski (ORCID: https://orcid.org/0000-0001-5599-8558)
- Minhaz Ud-Dean
- Eunike Sawitning Ayu Setyono (ORCID: https://orcid.org/0009-0008-1863-9028)
- Eckhard Wolf (ORCID: https://orcid.org/0000-0002-0430-9510)
- Elisabeth Kemter (ORCID: https://orcid.org/0000-0001-7785-7502)
- Katharina Scheibner (ORCID: https://orcid.org/0000-0002-3555-2417)
- James M. Wells (ORCID: https://orcid.org/0000-0002-1398-848X)
- Xinghao Zhang (ORCID: https://orcid.org/0000-0002-5472-3891)
- Hannah Spitzer (ORCID: https://orcid.org/0000-0002-7858-0936)
- Julie B. Sneddon (ORCID: https://orcid.org/0000-0002-7404-8598)
- Kaiyuan Yang (ORCID: https://orcid.org/0000-0002-5361-2620)
- Karin Hrovatin (ORCID: https://orcid.org/0000-0003-3319-9645)
- Angelika Schnieke (ORCID: https://orcid.org/0000-0002-5761-9635)
- Heiko Lickert (ORCID: https://orcid.org/0000-0002-4597-8825)
- Tatiana Flisikowska
- Thomas Walzthoeni
- Fabian Joachim Theis (ORCID: https://orcid.org/0000-0002-2419-1943)
- Barbara Keßler (ORCID: https://orcid.org/0000-0001-7036-238X)
Institutions
- Cincinnati Children's Hospital Medical Center (US)
- University of California, San Francisco (US)
- Helmholtz Zentrum München (DE)
- Weihenstephan-Triesdorf University of Applied Sciences (DE)
- Broad Center (US)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Heinrich Heine University Düsseldorf (DE)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-22
- DOI
- https://doi.org/10.1038/s41467-025-64774-4
- Citations
- 2
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 4.01
Funders
- Cincinnati Children's Hospital Medical Center
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Technische Universität München
- National Institutes of Health
- University of California, San Francisco
- Diabetes Center, University of California, San Francisco