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Single cell transcriptomics defines human islet cell signatures and reveals cell-type-specific expression changes in type 2 diabetes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE86473 | GEO | 2016/11/09

REPOSITORIES: GEO

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Single cell transcriptomics defines human islet cell signatures and reveals cell-type-specific expression changes in type 2 diabetes [bulk]

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

Single cell transcriptomics defines human islet cell signatures and reveals cell-type-specific expression changes in type 2 diabetes [single cell]

2016-11-09 | GSE86469 | GEO

Rhesus Macaque Model of Mismatch Repair-Deficient Colorectal Cancer

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

Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS

Project description:We perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression. David Pan was funded through Grant Title: Biomedical Big Data Training Grant Grant ID: T32LM012424 Funding Source: National Institutes of Health-National Cancer Institute Marcus Alvarez was funded through Grant Title: NIH training grant in Genomic Analysis and Interpretation Grant ID: T32HG002536 Funding Source: National Institutes of Health

2018-04-17 | GSE110619 | GEO

Carbon sources tune antibiotic susceptibility in Pseudomonas aeruginosa via TCA cycle control

Project description:This study examines the mechanisms underlying fumarate- and glyoxylate-mediated changes in tobraymcyin sensitivity in PAO1 cells Grant ID: NIH Grant K99 GM 118907 Grant title: Effects of Host Metabolic Variation on Antibiotic Susceptibility Funding Source: NIH NIGMS Name: Jason Yang

2016-12-20 | GSE90620 | GEO

Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes

Project description:Faithful meiotic chromosome inheritance and fertility relies on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs on chromosomes that have successfully initiated crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 Kb near all telomeres that escape DSB downregulation. These regions retain Hop1 and continue to break in pachynema despite normal synaptonemal complex deposition. Differential retention of Hop1 requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences, and is modulated by the histone deacetylase Sir2 and the nucleoporin Nup2. Importantly, the uniform size of EARs among chromosomes contributes to disproportionately high DSB and repair signals on short chromosomes in pachynema, suggesting that EARs partially underlie the curiously high recombination rate of short chromosomes. Grant ID: Research grant #6-FY16-208 Grant title: Meiotic segregation of small chromosomes Funding Source: March of Dimes Foundation Affiliation: NEW YORK UNIVERSITY Name: Andreas Hochwagen

2019-01-10 | GSE105111 | GEO

Effect of high-fat diet on hepatic DNA methylation in SM/J mice

Project description:We identified differentially methylated regions across the genome in the liver associated with a high-fat diet. Grant: Funding source: American Heart Association Grant number: 16PRE26420105 Title: The effect of maternal over-nutrition on obesity, epigenetics, and gene expression Awarded to Madeline Keleher

2018-11-26 | GSE122016 | GEO

Genome–wide gene expression profile of adipocytes and infiltration macrophages obtained from abdominal (visceral and subcutaneous) and peripheral (thigh) adipose depots from Normal Glucose Tolerant and Type 2 Diabetics Asian Indians

Project description:We have identified molecular-level alternations in different adipose depots (thigh, visceral and subcutaneous) of Asian Indians (both male and female) suffering from type-2 diabetes as compared to age and BMI matched normal glucose tolerant subjects by functional analysis of differentially expressed genes, and correlation of gene expression estimates with measured intermediate traits associated with T2D and its related co-morbidities (Hb1Ac, HOMA-B, HOMA-R, NEFA, Triglyceride, Total Cholesterol, HDL, LDL, VLDL, Leptin, Adiponectin, TNF-α, Serum- Creatinine, IL-6, High sensitivity - serum-creatinine (hs-CRP) and also size of adipocytes). Funding: Grant Id: 5/4/8/2012-RMC Grant title: Clinical, Biochemical and Cellular Correlates of Transcriptome of Adipose Tissue Among Type-2 Diabetics Name of the funding source: Indian Council for Medical Research

2018-12-31 | GSE78721 | GEO

Transcriptomics of xylem from a Populus deltoides population

Project description:We sequenced the xylem transcriptome from a population of unrelated individuals of P. deltoides to uncover a master regulator of lignin biosynthesis. Grant ID: IOS-1444543 Grant Title: Genome and transcriptome based prediction, and regulator inference, o molecular and whole-plant phenotypes. Funding source: NSF Plant Genome Research Program.

2020-05-04 | GSE140232 | GEO

Plasma miRNAs expression in acute ischemic stroke patients with or without recombinant tissue plasminogen activator treatment.

Project description:To determine the expression of circulating miRNAs in AIS patients with thrombolysis and without thrombolysis. Grant ID: 81100882 Grant title: The relation between transcription of miR-497 and neurons apoptosis after ischemic stroke Funding source: Chinese National Natural Science Foundation Grantee First Name: Zhen Grantee Last Name:Deng

2017-02-23 | GSE95204 | GEO

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