Project description:Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes. Endocrine cells age heterogeneously, complicating the effort to unravel the molecular drives underlying endocrine aging. To overcome these obstacles, we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys. Despite sex differences and increased single-cell level transcriptional variations, aged β-cells showed increased unfolded protein response (UPR) along with the accumulation of protein aggregates. We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling, comprising adaptive UPR during pancreatic aging. Notably, we found age-related β-cell-specific upregulation of HSP90B1, an ER-located chaperone, impeded high glucose-induced insulin secretion. Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at the single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis, suggesting an avenue for therapies to delay β-cell aging and prevent aging-related diabetes.

2020-06-11 | GSE120180 | GEO

Use of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells

Project description:This study provides an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combines microfluidic technology and nanoliter-scale reactions. We sequenced 622 cells allowing identification of 341 islet cells with high-quality gene expression profiles. The cells clustered into populations of alpha-cells (5%), beta-cells (92%), delta-cells (1%) and PP-cells (2%). We identified cell-type specific transcription factors and pathways primarily involved in nutrient sensing and oxidation and cell signaling. Unexpectedly, 281 cells had to be removed from the analysis due to low viability (23%), low sequencing quality (13%) or contamination resulting in the detection of more than one islet hormone (64%). Collectively, we provide a resource for identification of high-quality gene expression datasets to help expand insights into genes and pathways characterizing islet cell types. We reveal limitations in the C1 Fluidigm cell capture process resulting in contaminated cells with altered gene expression patterns. This calls for caution when interpreting single-cell transcriptomics data using the C1 Fluidigm system. Single-cell RNA sequencing of mouse C57BL/6 pancreatic islet cells

2016-02-19 | E-GEOD-77980 | biostudies-arrayexpress

Single-cell transcriptomics reveals unique features of human pancreatic islet cell subtypes

Project description:We report the single-cell RNA-seq based identification of 6 known human islet cell types (alpha cells, beta cells, delta cells, pp cells, acinar cells and duct cells) based on the expression of known marker genes. We further assess cell type specific gene expression and suggest novel marker genes for several cell types. Transcriptional dissection of human pancreatic islets of one donor using single-cell RNA-seq

2016-01-05 | E-GEOD-73727 | biostudies-arrayexpress

Single-cell sequencing of gene expression profiles comparing murine skin at E14.5, E17.5, P5 WT.

Project description:Gene expression at single-cell level 10X Genomics of whole skin collected from WT E14.5, E17.5, and P5 mice.

2023-06-15 | GSE227257 | GEO

Understanding oxidative stress responses in pancreatic islet cells by single cell RNA-sequencing analysis

Project description:We found these ROS generation is regulated by lncRNA MALAT1 and genetic ablation of MALAT1 drastically reduced ROS level and oxidative stress in mouse islet cells with the benefits of improved insulin responses in MALAT1-/- mouse. The pancreatic islet consists of five cell types (α, β and γ/PP, δ and ε cells) and very little is known about the xenobiotic detoxification pathways in these cells and their sensitivity to toxicants. We utilized single-cell RNA sequencing to analyze the role of MALAT1 in regulating oxidative stress response and insulin secretion function in distinct pancreatic cell population. We also treat the isolated pancreatic islets with 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (10 nM, 12h) to investigate the xenobiotic detoxification pathways regulation in both MALAT1 KO and WT pancreatic islets. Our result showed that a subset of genes in T2DM related pathways were significantly regulated in MALAT1 -/- β cells, with significantly unregulated INS1, INS2, and PDX1. Nrf2/detoxification pathway was also significantly activated in MALAT1 -/- β cells. In addition, MALAT1 expression level was elevated in the T2DM patients pancreatic islets cells. This study provides insights for mechanisms of regulation of oxidative stress by MALAT1-Nrf2 interaction which has the potential as a therapeutic target for the treatment of T2DM.

2021-05-28 | GSE166391 | GEO

A Single-cell Transcriptomic Atlas of Primate Pancreatic Islet Aging

Project description:A Single-cell Transcriptomic Atlas of Primate Pancreatic Islet Aging

| PRJNA491895 | ENA