Science advances · 2025
Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs of type 1 diabetes progression.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Melton Rebecca, Jimenez Sara, Elison Weston, Tucciarone Luca, Howell Abigail, Wang Gaowei, Berti Denise, Beebe Elisha, Miller Michael, Zeng Chun, McGrail Carolyn, VanderStel Kennedy, Korgaonkar Katha, Elgamal Ruth, Mummey Hannah, Chiou Joshua, Griffin Emily, Kusmartseva Irina, Atkinson Mark, Preissl Sebastian, Theis Fabian J, Sander Maike, Gaulton Kyle J
Аннотация
Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here, we performed single-nucleus multiomics and spatial transcriptomics in up to 32 nondiabetic (ND), autoantibody-positive (AAB+), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine subtypes. β, Acinar, and other cell types, and related cellular niches, had altered abundance and gene activity in T1D progression, including distinct pathways altered in AAB+ compared to T1D. We identified epigenomic drivers of gene activity in T1D and AAB+ which, combined with genetic association, revealed causal pathways of T1D risk including antigen presentation in β cells. Last, single-cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting β cell regulation. Overall, these results revealed drivers of T1D in the pancreas, which form the basis for therapeutic targets for disease prevention.