ArticleGenome medicine2023
Single-nucleus RNA sequencing of human pancreatic islets identifies novel gene sets and distinguishes β-cell subpopulations with dynamic transcriptome profiles.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Single-Cell Meta-Analysis Uncovers the Pancreatic Endothelial Cell Transcriptomic Signature and Reveals a Key Role for NKX2-3 in PLVAP Expression.Arteriosclerosis, thrombosis, and vascular biology · 2024Pooled it
- Insulin receptor signaling in gustatory cells suppresses sugar taste sensitivity and feeding iniScience · 2026Article
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Single-cell profiling of pancreatic islets maps subtype-associated molecular alterations in type 2 diabetes.Diabetologia · 2026Article
- GPR180 deficiency impairs mitochondrial function and insulin secretion in pancreatic β-cells.Molecular metabolism · 2026Article
- The challenges of single cell transcriptomics on difficult human tissue: the placenta.NAR genomics and bioinformatics · 2026Article
- Long QT syndrome and hypoglycemia in a postbariatric surgery patient with a likely pathogenic variant inJCEM case reports · 2026Article
- Activation of the Pancreatic "Metabolic Synapse" Aggravates Type 2 Diabetes Mellitus by Inducing PANoptosis in β-Cells.Diabetes · 2026Article
- Activated Human Pancreatic Stellate Cells SignatureCommunication in Type 1 Diabetes.Research square · 2026Article
- Emerging roles of circular RNAs and enhancer RNAs: new insights into the development and management of neurodegenerative disorders.Biomarker research · 2026Review
- DOCK10 Regulates Insulin Hypersecretion in Insulinoma and Serves as a Diagnostic and Therapeutic Target.Cellular and molecular gastroenterology and hepatology · 2026Article
- α-cell SLC38A5 supports amino acid-induced α-cell proliferation and glucagon secretion.Frontiers in endocrinology · 2026Article
- Decoding adult murine pancreatic islet cell diversity through cell type-resolved proteomics and phosphoproteomics.Communications biology · 2025Article
- Evaluating cell-specific gene expression using single-cell and single-nuclei RNA-sequencing data from human pancreatic islets of the same donors.Scientific reports · 2025Article
- Human pancreatic α-cell heterogeneity and trajectory inference analyses reveal SMOC1 as a β-cell dedifferentiation gene.Nature communications · 2025Article
- Latent plasticity of the human pancreas across development, health, and disease.bioRxiv : the preprint server for biology · 2025Article
- The role of the beta cell in type 2 diabetes: new findings from the last 5 years.Diabetologia · 2025Review
- Article
- Interpretable machine learning-guided single-cell mapping deciphers multi-lineage pancreatic dysregulation in type 2 diabetes.Cardiovascular diabetology · 2025Article
- Integrating Spatial and Single-Nucleus Transcriptomic Data to Assess the Effects of Intrauterine Hyperglycemia on Fetal Pancreatic Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundSingle-cell RNA sequencing (scRNA-seq) provides valuable insights into human islet cell types and their corresponding stable gene expression profiles. However, this approach requires cell dissociation that complicates its utility in vivo. On the other hand, single-nucleus RNA sequencing (snRNA-seq) has compatibility with frozen samples, elimination of dissociation-induced transcriptional stress responses, and affords enhanced information from intronic sequences that can be leveraged to identify pre-mRNA transcripts.
methodsWe obtained nuclear preparations from fresh human islet cells and generated snRNA-seq datasets. We compared these datasets to scRNA-seq output obtained from human islet cells from the same donor. We employed snRNA-seq to obtain the transcriptomic profile of human islets engrafted in immunodeficient mice. In both analyses, we included the intronic reads in the snRNA-seq data with the GRCh38-2020-A library.
resultsFirst, snRNA-seq analysis shows that the top four differentially and selectively expressed genes in human islet endocrine cells in vitro and in vivo are not the canonical genes but a new set of non-canonical gene markers including ZNF385D, TRPM3, LRFN2, PLUT (β-cells); PTPRT, FAP, PDK4, LOXL4 (α-cells); LRFN5, ADARB2, ERBB4, KCNT2 (δ-cells); and CACNA2D3, THSD7A, CNTNAP5, RBFOX3 (γ-cells). Second, by integrating information from scRNA-seq and snRNA-seq of human islet cells, we distinguish three β-cell sub-clusters: an INS pre-mRNA cluster (β3), an intermediate INS mRNA cluster (β2), and an INS mRNA-rich cluster (β1). These display distinct gene expression patterns representing different biological dynamic states both in vitro and in vivo. Interestingly, the INS mRNA-rich cluster (β1) becomes the predominant sub-cluster in vivo.
conclusionsIn summary, snRNA-seq and pre-mRNA analysis of human islet cells can accurately identify human islet cell populations, subpopulations, and their dynamic transcriptome profile in vivo.
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