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Plate IV.72 · Publications

A multimodal cross-species comparison of pancreas development

Article in Nature Communications, 22 October 2025.

Open accessStem Cells, Lineage

  1. Kaiyuan Yang
  2. Hannah Spitzer
  3. Michael Sterr
  4. Karin Hrovatin
  5. Sean de la O
  6. Xinghao Zhang
  7. Eunike Sawitning Ayu Setyono
  8. Minhaz Ud-Dean
  9. Thomas Walzthoeni
  10. Krzysztof Flisikowski
  11. Tatiana Flisikowska
  12. Angelika Schnieke
  13. Katharina Scheibner
  14. James M. Wells
  15. Julie B. Sneddon
  16. Barbara Kessler
  17. Eckhard Wolf
  18. Elisabeth Kemter
  19. Fabian J. Theis
  20. Heiko Lickert

Abstract

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.

Versions2

  1. PublishedNature Communications10.1038/s41467-025-64774-4
  2. PreprintResearch Square10.21203/rs.3.rs-4151759/v1

Cite

@article{yang2025multimodal,
  title = {{A multimodal cross-species comparison of pancreas development}},
  author = {Yang, Kaiyuan and Spitzer, Hannah and Sterr, Michael and Hrovatin, Karin and de la O, Sean and Zhang, Xinghao and Setyono, Eunike Sawitning Ayu and Ud-Dean, Minhaz and Walzthoeni, Thomas and Flisikowski, Krzysztof and Flisikowska, Tatiana and Schnieke, Angelika and Scheibner, Katharina and Wells, James M. and Sneddon, Julie B. and Kessler, Barbara and Wolf, Eckhard and Kemter, Elisabeth and Theis, Fabian J. and Lickert, Heiko},
  journal = {Nature Communications},
  publisher = {Springer Science and Business Media LLC},
  year = {2025},
  month = oct,
  doi = {10.1038/s41467-025-64774-4},
  url = {https://doi.org/10.1038/s41467-025-64774-4},
  pmid = {41125606},
  pmcid = {PMC12546597}
}
.bib file