A single-cell multi-omic atlas of the human pancreas reveals potential for cellular plasticity across development, health, and disease.
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Mereu E, Balboa D, Liebig J, Gonzalez-Herrero A, Casals AM, Mardamshina M, Mollandin F, Schicktanz F, Sudy A, Tosti L, van Agen M, Vandenbempt V, Avrahami D, Navarro FB, Bernardo E, Björklund F, Chua RL, Engelse M, García-Hurtado J, Groen N, Hanegraaf M, Iañez P, Jechow K, Konukiewitz B, Lawerenz C, Lewandowski-Hoppe N, Marchese D, Muraro MJ, Pellegrini S, Sordi V, Taron U, Ten FW, Trefzer T, Twardziok S, Wirth J, Carlotti F, de Koning E, Ferrer J, Glaser B, Heyn H, Lundberg E, Piemonti L, Steiger K, van Oudenaarden A, Weichert W, Conrad C, Eils R
Cell Metab. - (-) - [2026-08-12; online 2026-08-12]
The pancreas plays a central role in major human diseases, yet our understanding of its cellular diversity and plasticity remains incomplete. Here, we present a single-cell multiomics atlas of the human pancreas, profiling over four million cells and nuclei from 57 donors across fetal development, adult homeostasis, and type 2 diabetes (T2D). Integrating single-cell RNA sequencing (scRNA-seq)/single-nucleus RNA sequencing (snRNA-seq), snATAC-seq, VASA-seq, spatial transcriptomics (Xenium), and multiplexed proteomics (CODEX), we resolve gene expression, chromatin accessibility, and spatial organization at high resolution. We identify transcriptionally plastic centroacinar-like cells (pCACs) in adults with fetal-like features, delineate endocrine and exocrine lineage trajectories during development, and define HNF1A-defined beta cell epigenetic states. In T2D, we observe shifts in beta cell subtypes and altered regulatory programs. Glucose perturbation of healthy islets reveals cell-type-specific adaptation and stress responses. This atlas provides a foundational framework to understand pancreas biology and the role of cellular plasticity in regeneration and disease.
PubMed 42586061
DOI 10.1016/j.cmet.2026.07.023
Crossref 10.1016/j.cmet.2026.07.023
pii: S1550-4131(26)00296-2