Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell transcriptomics of East-Asian pancreatic islets cells

ABSTRACT: Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on α- and β-cell gene expression in mice and subjects of predominantly European ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. Differentially expressed transcripts between α- and β-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed. We identified 118 α, 105 β, 6 δ endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed differential expression between α- and β-cells. 10 genes showed concordant expression as reported in rodents, while FAM46A was significantly discordant. Comparing our East-Asian data with data from primarily European subjects, we replicated several genes implicated in nuclear receptor activations, acute phase response pathway, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR signaling. Additionally, we identified protein ubiquitination to be associated among East-Asian β-cells. We report on East-Asian α- and β-cell gene signatures and substantiate several genes/pathways. We identify expression signatures in East-Asian β-cells that perhaps reflects increased susceptibility to cell-death and warrants future validations to fully appreciate their role in East-Asian diabetes pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97655 | GEO | 2017/08/11

SECONDARY ACCESSION(S): PRJNA382566

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

MERLION LUNG CANCER STUDY_2_DNA

Project description:East-Asian (EA) patients with Non Small Cell Lung Cancer (NSCLC) are associated with a high proportion of non-smoking women, EGFR activating somatic mutations, and clinical responses to tyrosine kinase inhibitors. We identify copy number alterations specific to EA and Western European (WE) NSCLCs and conducted an integrative analysis using transcritomic data for identifying copy-number-driven candidate genes. Samples were hybridized to Affymetrix Genome-Wide Human SNP 6.0 arrays according to the manufacturer’s specifications in the same center. 226 lung adenocarcinomas (90 East-Asian and 136 Western-European) were analyzed for copy-number aberrations (CNAs) using a common high resolution SNP microarray platform.

2011-11-22 | E-GEOD-33848 | biostudies-arrayexpress

Gene expression breast cancer

Project description:There exists a common deletion polymorphism on the genetic loci of APOBEC3B and this polymorphism exist in ~37% of East Asians and ~7% of Europeans. Germline APOBEC3B deletion has bee27233495n shown to confer modest risk to breast cancer in both East Asian women and women of European descent We performed expression profiling by array to investigate the significantly differentially expressed genes and enriched gene sets in APOBEC3B-null vs. APOBEC3B breast cancers

2016-09-18 | GSE73540 | GEO

Converting adult pancreatic α-cells into β-cells by targeting Dnmt1 and Arx

Project description:After their destruction in adult mice, insulin-producing pancreatic beta-cells slowly regenerate from other islet cells, like glucagon-producing alpha-cells. However the molecular basis of this conversion is unknown. Moreover it remains unclear if this intra-islet cell conversion is relevant to human diseases with extensive beta-cell loss, like in type 1 diabetes (T1D). Here, we show that subsets of glucagon-expressing cells in subjects with T1D produce Insulin and other molecular features of beta-cells, accompanied by loss of the alpha-cell regulators DNA methyltransferase 1 (Dnmt1) and Aristaless-related homeobox (Arx). We generated mice permitting lineage tracing and inactivation of Dnmt1 and Arx in adult alpha-cells. Within 3 months of Dnmt1 and Arx loss, 50% of alpha-cells converted into cells producing insulin protein but not glucagon, changes not observed in alpha-cells after only Arx or Dnmt1 loss. Single cell isolation and high-throughput RNA sequencing revealed efficient and extensive alpha-cell conversion into progeny indistinguishable by global gene expression from native beta-cells. Our work reveals pathways regulated by Arx and Dnmt1 sufficient for achieving targeted generation of beta-cells from adult pancreatic alpha-cells.

2017-02-16 | GSE79457 | GEO

MERLION LUNG CANCER STUDY_2_DNA

2011-11-22 | GSE33848 | GEO

Combinatorial transcription factor profiles predict mature and functional human islet α and β cells

Project description:Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled >40,000 cells from normal human islets by scRNA-seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells co-expressing ARX/MAFB (α cells) and MAFA/MAFB (β cells) exhibited greater expression of key genes related to glucose sensing and hormone secretion relative to subpopulations expressing only one or neither TF. Moreover, all subpopulations were identified in native pancreatic tissue from multiple donors. By Patch-seq, MAFA/MAFB co-expressing β cells showed enhanced electrophysiological activity. Thus, these results indicate combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations.

2021-09-09 | GSE183568 | GEO

Single cell transcriptomics of human islet ontogeny defines the molecular basis of beta cell dedifferentiation in T2D

Project description:Dedifferentiation of pancreatic beta cells may reduce islet function in type 2 diabetes (T2D). However, the prevalence, plasticity and functional consequences of this cellular state remain unknown. We employed single-cell RNAseq to detail the maturation program of alpha and beta cells during human ontogeny. We show that although both alpha and beta cells mature in part by repressing non-endocrine genes, alpha-cells retain hallmarks of an immature state, while beta-cells attain a full beta-cell specific gene expression program. In islets from T2D donors, both alpha- and beta-cells return to a less mature expression profile, de-repressing the juvenile genetic program and exocrine genes while increasing expression of exocytosis, inflammation and stress response signaling pathways. These changes support the increased proportion of beta-cells displaying suboptimal function observed in T2D islets. These findings provide new insights into the molecular program underlying islet cell maturation during human ontogeny and the loss of transcriptomic maturity that occurs in islets of type 2 diabetics.

2020-10-01 | GSE154126 | GEO

Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming

Project description:Insulin-secreting β cells and glucagon-secreting α cells maintain physiological blood glucose levels, and their malfunction drives diabetes development. Using ChIP sequencing and RNA sequencing analysis, we determined the epigenetic and transcriptional landscape of human pancreatic α, β, and exocrine cells. We found that, compared with exocrine and β cells, differentiated α cells exhibited many more genes bivalently marked by the activating H3K4me3 and repressing H3K27me3 histone modifications. This was particularly true for β cell signature genes involved in transcriptional regulation. Remarkably, thousands of these genes were in a monovalent state in β cells, carrying only the activating or repressing mark. Our epigenomic findings suggested that α to β cell reprogramming could be promoted by manipulating the histone methylation signature of human pancreatic islets. Indeed, we show that treatment of cultured pancreatic islets with a histone methyltransferase inhibitor leads to colocalization of both glucagon and insulin and glucagon and insulin promoter factor 1 (PDX1) in human islets and colocalization of both glucagon and insulin in mouse islets. Thus, mammalian pancreatic islet cells display cell-type–specific epigenomic plasticity, suggesting that epigenomic manipulation could provide a path to cell reprogramming and novel cell replacement-based therapies for diabetes. Pancreatic islets were collected post-mortem from 6 human donors and subjected to FACS to separate populations of alpha, beta, and exocrine cells. Depending on the availability of resulting material, sorted islet cell populations were used for H3K4me3, H3K27me3 ChIP-seq, or RNA-seq analysis. All ChIP-seq samples have a corresponding input from the same sample.

2013-08-28 | E-GEOD-50386 | biostudies-arrayexpress

Pancreatic alpha and beta-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression

Project description:We performed a parallel analysis of the molecular properties of α- and β-cell oscillators, using a mouse model expressing three reporter genes: one labeling α-cells, one specific for β-cells, and a third monitoring circadian gene expression. Diurnal transcriptome analysis in separated α- and β-cells revealed that a high number of genes with key roles in islet physiology, including regulators of glucose sensing and hormone secretion, are differentially expressed in these cell types. This study represents the first parallel large-scale circadian in vivo transcriptome analysis in separated α- and β-cells.

2017-02-22 | GSE95156 | GEO

Alpha TC1 and Beta-TC-6 genomic profiling uncovers both shared and distinct transcriptional regulatory features with their primary islet counterparts

Project description:Alpha TC1 (αTC1) and Beta-TC-6 (βTC6) mouse islet cell lines are cellular models of islet (dys)function and type 2 diabetes (T2D). However, genomic characteristics of these cells, and their similarities to primary islet alpha and beta cells, are undefined. Here, we report the epigenomic (ATAC-seq) and transcriptomic (RNA-seq) landscapes of αTC1 and βTC6 cells. Each cell type exhibits hallmarks of its primary islet cell counterpart including cell-specific expression of beta (e.g., Pdx1) and alpha (e.g., Arx) cell transcription factors (TFs), and enrichment of binding motifs for these TFs in αTC1/βTC6 cis-regulatory elements. αTC1/βTC6 transcriptomes overlap significantly with the transcriptomes of primary mouse/human alpha and beta cells. Our data further indicate that ATAC-seq detects cell-specific regulatory elements for cell types comprising ≥ 20% of a mixed cell population. We identified αTC1/βTC6 cis-regulatory elements orthologous to those containing type 2 diabetes (T2D)-associated SNPs in human islets for 33 loci, suggesting these cells’ utility to dissect T2D molecular genetics in these regions. Together, these maps provide important insights into the conserved regulatory architecture between αTC1/βTC6 and primary islet cells that can be leveraged in functional (epi)genomic approaches to dissect the genetic and molecular factors controlling islet cell identity and function.

2017-09-20 | GSE99954 | GEO

RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes

Project description:Pancreatic islet cells are critical for maintaining normal blood glucose levels and their malfunction underlies diabetes development and progression. We used single-cell RNA sequencing to determine the transcriptomes of 1,492 human pancreatic α-, β-, δ- and PP cells from non-diabetic and type 2 diabetes organ donors. We identified cell type specific genes and pathways as well as 245 genes with disturbed expression in type 2 diabetes. Importantly, 92% of the genes have not previously been associated with islet cell function or growth. Comparison of gene profiles in mouse and human α- and β-cells revealed species-specific expression. All data are available for online browsing and download and will hopefully serve as a resource for the islet research community.

2016-08-31 | GSE81608 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data