{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329967/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Mus musculus"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"," Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329967"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Temporal Single-Cell Transcriptional Dynamics of Murine Pancreatic Islet Remodeling During Hyperglycaemia Progression","description":"Pancreatic islets undergo coordinated cellular remodeling during obesity-induced insulin resistance. However, longitudinal changes across endocrine and non-endocrine compartments remain largely unexplored. We present a comprehensive high-resolution atlas using longitudinal single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on islets from C57BL/6 mice subjected to high-fat diet (HFD) feeding for 8, 16, and 24 weeks, along with age-matched controls on regular chow (RC). We mapped dynamic changes in islet cell composition and transcriptional states. Trajectory inference indicated diversification of beta-cell programs into adaptive and inflammatory states under HFD. Progression of insulin resistance induced shrinkage and transcriptional remodeling of glucagon-secreting alpha-cells, marked by upregulation of genes related to intracellular transport and oxidative stress, accompanied by the emergence of a polyhormonal alpha-cell subpopulation. Similarly, we identified delta-cell subpopulations exhibiting beta-like transcriptional signatures and polyhormonal identity under nutritional stress, suggesting adaptive delta-cell plasticity that may partially compensate for beta-cell loss during insulin resistance. The islet microenvironment exhibited robust expansion of proinflammatory M1 macrophages, reaching a plateau by 16 weeks of HFD, indicating niche saturation. Cell-cell communication analyses revealed disruption of key signaling pathways within endocrine and between endocrine and non-endocrine cells under HFD conditions. Notably, CCL27a–chemokine receptor signaling between beta-cells and M1 macrophages was significantly reduced in HFD islets, likely driven by reduced Ccl27a expression and chromatin accessibility in a distinct beta cell subpopulation, which we further validated using INS-1 cells exposed to HFD-like conditions. Comparative analysis with scRNA seq of human islets confirmed conserved stress signatures. Furthermore, genetic variants at the CCL27 locus were associated with increased T2D risk and HOMA-IR in human populations, establishing a novel link between beta-cell stress and systemic inflammation. This resource provides a hierarchical framework for understanding islet failure and identifies potential therapeutic nodes for type 2 diabetes.","dates":{"publication":"2026/05/25"},"accession":"GSE329967","cross_references":{"GSM":["GSM9714179","GSM9714178","GSM9714191","GSM9714190","GSM9714193","GSM9714171","GSM9714170","GSM9714192","GSM9714173","GSM9714194","GSM9714172","GSM9714175","GSM9714174","GSM9714177","GSM9714176","GSM9714168","GSM9714167","GSM9714189","GSM9714169","GSM9714180","GSM9714182","GSM9714181","GSM9714184","GSM9714162","GSM9714183","GSM9714164","GSM9714186","GSM9714185","GSM9714163","GSM9714188","GSM9714166","GSM9714187","GSM9714165"],"GPL":["21103","24247"],"GSE":["329967"],"taxon":["Mus musculus"]}}