Single cell transcriptomics defines human islet cell signatures and reveals cell-type-specific expression changes in type 2 diabetes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE86473 | GEO | 2016/11/09
REPOSITORIES: GEO
Similar Datasets
Project description:Blood glucose levels are tightly controlled by the coordinated action of at least five cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 diabetes (T2D). Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet dysfunction, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single cell transcriptomes for 617 islet cells after profiling ~1000 cells from non-diabetic (ND) and T2D human organ donors. Analyses of non-diabetic single cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell type-specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis. Grant ID: Award No. W81XWH-16-1-0130 Grant title: Peer Reviewed Medical Research Program Funding Source: Assistant Secretary of Defense for Health Affairs Affiliation: Jackson Laboratory for Genomic Medicine, Farmington, CT Name: Michael Stitzel
2016-11-09 | GSE86468 | GEO
Project description:Blood glucose levels are tightly controlled by the coordinated action of at least five cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 diabetes (T2D). Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet dysfunction, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single cell transcriptomes for 617 islet cells after profiling ~1000 cells from non-diabetic (ND) and T2D human organ donors. Analyses of non-diabetic single cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell type-specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis. Grant ID: Award No. W81XWH-16-1-0130 Grant title: Peer Reviewed Medical Research Program Funding Source: Assistant Secretary of Defense for Health Affairs Affiliation: Jackson Laboratory for Genomic Medicine, Farmington, CT Name: Michael Stitzel
2016-11-09 | GSE86469 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. NIH grant(s): Grant ID: 5 P30 CA016672-44 Grant title: Cancer Center Support Grant Affiliation: The University of Texas MD Anderson Cancer Center Grantor: NCI
2022-03-31 | GSE178383 | GEO
Project description:FUNGAL PLANET: A Peer-Reviewed Global Initiative to Promote the Study of Fungal Biodiversity.
| PRJEB28837 | ENA
Project description:To determine differences in GC Tfh cells isolated from the tonsils of children who have undergone tonsillectomy for either recurrent Group A Streptococcus (GAS) tonsillitis (RT) or non-RT (sleep apnea). Grants: Thrasher Research Fund for an Early Career Award 12969 - Jennifer Dan UM1 AI100663 - Shane Crotty Clinical Research Fellowship Grant UK Charity No. 1089464 - David Layfield, Ramsey Cuttress, Christian Ottensmeier
2019-06-20 | GSE123977 | GEO
Project description:Colorectal cancer (CRC) remains the third most common cancer in the US, with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1. DNA methylation and transcriptome analysis was used to evaluate the rhesus macaque as a model organism to study carcinogenesis, develop immunotherapies and vaccines, and implement chemoprevention approaches pertinent to sporadic MSI-H and LS CRC in humans. NIH grant(s): Grant ID: 5 P30 CA016672-44 Grant title: Cancer Center Support Grant Affiliation: The University of Texas MD Anderson Cancer Center Grantor: NCI
2022-03-31 | GSE178381 | GEO
Project description:Colorectal cancer (CRC) remains the third most common cancer in the US, with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1. DNA methylation and transcriptome analysis was performed to evaluate the rhesus macaque as a model organism to study carcinogenesis, develop immunotherapies and vaccines, and implement chemoprevention approaches pertinent to sporadic MSI-H and LS CRC in humans. NIH grant(s): Grant ID: 5 P30 CA016672-44 Grant title: Cancer Center Support Grant Affiliation: The University of Texas MD Anderson Cancer Center Grantor: NCI
2022-03-31 | GSE178377 | GEO
Project description:Plants sense light and temperature changes to regulate flowering time. The expression of the florigen gene, FLOWERING LOCUS T (FT), peaks in the morning during spring, a different pattern than we observe in the lab. Providing our lab growth conditions with a red/far-red light ratio similar to open field conditions and average natural temperature oscillation is sufficient to mimic the FT expression and flowering time in natural long days. Here, we use RNA-seq to identify and understand the molecular differences between natural growth conditions, conventional lab growth conditions, and supplemented lab growth conditions that mimic natural conditions. Non-NIH grant(s): Grant ID: NSF 1656076 Grant title: Exploring Seasonal Flowering Mechanisms Affiliation: University of Washington Name: Takato Imaizumi
2018-04-01 | GSE110605 | GEO
Project description:GL261 cells are a widely-used model system for glioma tumors and can be cultured adherently or as free-floating cell aggregates known as neurospheres. Neurospheres can be implanted into mice where they readily form tumors. This suggests that neurospheres may more closely resemble the in-vivo tumor phenotype. Our study has two primary objectives: 1) To determine differences in gene expression between adherent cells and the tumor-forming neurospheres and 2) To determine the extent of homogeneity in these cell populations. This project was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (Grant #P20GM103408) along with a Murdock College Science Research Program Grant (SR-202119904) from the M.J. Murdock Charitable Trust.
2025-08-18 | GSE277850 | GEO
Project description:HiCUP is a pipeline for processing sequence data generated by Hi-C, a technique used to investigate the three-dimensional organisation of a genome. The pipeline maps data to a specified reference genome and removes artefacts that would otherwise hinder subsequent analysis. HiCUP also provides an easy-to-interpret yet detailed quality control report that may be used by researchers to refine their experimental protocol for future studies. The software is freely available and has already been used for processing Hi-C data in several recently published peer-reviewed research articles. This experiment investigates the impact of using HiCUP to remove putative PCR amplification products in heavily duplicated Capture Hi-C libraries.
2015-10-29 | GSE73204 | GEO