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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, 20:9355 (2025)
Verlagsversion Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Beta-cells; Insulin-secretion; Islet Development; Target Genes; Identification; Expression; Mice; Maturation
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 16, Heft: 1, Seiten: 20, Artikelnummer: 9355 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) 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
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e) G-502300-001
G-503800-001
G-501900-231
A-632700-001
Förderungen European Research Council
German Research Foundation
Juvenile Diabetes Research Foundation
German Federal Ministry of Education and Research
National Institutes of Health
Kraft Family Fellowship
DOI 10.1038/s41467-025-64774-4
WOS ID 001599930900022
Scopus ID 105019549591
PubMed ID 41125606
Erfassungsdatum 2025-10-24
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