A single-cell multi-omic atlas of the human pancreas integrating scRNA-seq, snRNA-seq, snATAC-seq, VASA-seq, spatial transcriptomics (Xenium), and multiplexed proteomics (CODEX) across >4 million cells/nuclei from 57 donors spanning fetal development, adult homeostasis, and type 2 diabetes (T2D).
The atlas identifies transcriptionally plastic centroacinar-like cells (pCACs) with fetal-like features in adults, defines HNF1A-driven beta cell epigenetic states, and reveals shifts in beta cell subtypes and altered regulatory programs in T2D; glucose perturbation of healthy islets further uncovers cell-type-specific stress and adaptation responses.
Cross-sectional donor design limits causal inference about disease progression; findings in isolated/profiled islets and tissue may not fully reflect in vivo dynamics; the atlas is descriptive and functional validation of identified plastic cell states (e.g., pCACs) is not yet provided.
This atlas reveals that adult human pancreatic cells retain fetal-like plasticity and that beta cell epigenetic and subtype heterogeneity is altered in T2D — findings that may guide future regenerative and precision therapeutic strategies, though direct clinical application awaits functional validation.
