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Yang, K. ; Spitzer, H. ; Sterr, M. ; Hrovatin, K. ; de la O, S.* ; Zhang, X.* ; Setyono, E.S.A. ; Ud-Dean, M. ; Walzthoeni, T. ; Flisikowski, K.* ; Flisikowska, T.* ; Schnieke, A.* ; Scheibner, K. ; Wells, J.M.* ; Sneddon, J.B.* ; Kessler, B.* ; Wolf, E.* ; Kemter, E.* ; Theis, F.J. ; Lickert, H.

A multimodal cross-species comparison of pancreas development.

Nat. Commun. 16:9355 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 16, Issue: 1, Pages: , Article Number: 9355 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Institute of Computational Biology (ICB)
CF Genomics (CF-GEN)
POF-Topic(s) 30201 - Metabolic Health
30205 - Bioengineering and Digital Health
90000 - German Center for Diabetes Research
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP Element(s) G-502300-001
G-503800-001
G-501900-231
A-632700-001
DOI 10.1038/s41467-025-64774-4
Scopus ID 105019549591
PubMed ID 41125606
Erfassungsdatum 2025-10-24
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