ArticleCell reports2025
Integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D-associated genes and regulatory signals.
Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- ProtectiveiScience · 2026Article
- PanKbase Integrated Single-Cell Map: A Comprehensive Atlas of Human Pancreatic Islets.bioRxiv : the preprint server for biology · 2026Article
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- Genetic association and machine learning improve the prediction of type 1 diabetes risk.Nature genetics · 2026Article
- Whole-genome CRISPR screening identifies genetic modifiers of stem cell-derived islet transplantation.Stem cells translational medicine · 2026Article
- Immune signaling as a determinant of cellular identity and tissue function.Frontiers in immunology · 2026Review
- Stress-driven remodeling of antigen presentation and chemokine signaling in pancreatic β-cells: implications for type 1 diabetes.Frontiers in immunology · 2026Review
- Identification of type 2 diabetes- and obesity-associated human β-cells using deep transfer learning.eLife · 2025Article
- Illuminating diabetesWorld journal of diabetes · 2025Review
- Single-cell decoding of human islet cell type-specific alterations in type 2 diabetes reveals converging genetic- and state-drivenbioRxiv : the preprint server for biology · 2025Article
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- Untangling the genetics of beta cell dysfunction and death in type 1 diabetes.Molecular metabolism · 2024Review
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23 authors.
Funding
Abstract
Genome-wide association studies (GWASs) have identified over 100 signals associated with type 1 diabetes (T1D). However, it has been challenging to translate any given T1D GWAS signal into mechanistic insights, such as causal variants, their target genes, and the specific cell types involved. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in human pancreatic islets under baseline and T1D-stimulating conditions. We nominate effector cell types for all T1D GWAS signals and the regulatory elements and genes for three independent T1D signals acting through β cells at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we validated the functional impact of these genes and regulatory regions using isogenic human embryonic stem cells (hESCs). We found that loss of RASGRP1 or DLK1, as well as disruption of their corresponding regulatory regions, led to increased β cell apoptosis. Furthermore, β cells derived from isogenic hESCs carrying the T1D risk allele of rs3783355 associated with DLK1 showed elevated β cell death. Through additional RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses, we identified five genes upregulated in both RASGRP1
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