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Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs of type 1 diabetes progression

By: Rebecca Melton · Sara Jimenez · Weston Elison · Luca Tucciarone · Abigail Howell · Gaowei Wang · Denise Berti · Elisha Beebe · Michael Miller · Chun Zeng · Carolyn McGrail · Kennedy VanderStel · Katha Korgaonkar · Ruth Elgamal · Hannah Mummey · Joshua Chiou · Emily Griffin · Irina Kusmartseva · Mark Atkinson · Sebastian Preissl · Fabian J Theis · Maike Sander · Kyle J Gaulton

10 September 2025 at 18:00

Sci Adv. 2025 Sep 12;11(37):eady0080. doi: 10.1126/sciadv.ady0080. Epub 2025 Sep 10.

ABSTRACT

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.

PMID:40929272 | PMC:PMC12422192 | DOI:10.1126/sciadv.ady0080

Single-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs driving type 1 diabetes progression

(Multiomics OR Omics) AND (Pancreatic)

3 March 2025 at 19:00

bioRxiv [Preprint]. 2025 Feb 17:2025.02.13.637721. doi: 10.1101/2025.02.13.637721.

ABSTRACT

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 non-diabetic (ND), autoantibody-positive (AAB+), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine sub-types. Beta, 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 beta cells. Finally, single cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting beta cell regulation. Overall, these results revealed drivers of T1D progression in the pancreas, which form the basis for therapeutic targets for disease prevention.

PMID:40027657 | PMC:PMC11870426 | DOI:10.1101/2025.02.13.637721