GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329967/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329967GEOGSEfalseTemporal Single-Cell Transcriptional Dynamics of Murine Pancreatic Islet Remodeling During Hyperglycaemia ProgressionPancreatic 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.2026/05/25GSE329967GSM9714179GSM9714178GSM9714191GSM9714190GSM9714193GSM9714171GSM9714170GSM9714192GSM9714173GSM9714194GSM9714172GSM9714175GSM9714174GSM9714177GSM9714176GSM9714168GSM9714167GSM9714189GSM9714169GSM9714180GSM9714182GSM9714181GSM9714184GSM9714162GSM9714183GSM9714164GSM9714186GSM9714185GSM9714163GSM9714188GSM9714166GSM9714187GSM97141652110324247329967Mus musculus