Comprehensive transcriptomes of mouse pancreatic islet delta, beta, and alpha cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE80673 | GEO | 2016/06/26
SECONDARY ACCESSION(S): PRJNA319646
REPOSITORIES: GEO
Similar Datasets
Project description:Rodent models are widely used to study diabetes. Yet, significant gaps remain in our understanding of mouse islet physiology. We generated comprehensive transcriptomes of mouse delta, beta and alpha cells using two separate triple transgenic mouse models generated for this purpose. This enables systematic comparison across thousands of genes between the three major endocrine cell types of the islets of Langerhans whose principal hormones control nutrient homeostasis. FACS purified delta or alpha cells and beta cells from the same islets. Islets were isolated from triple transgenic offspring of a cross between mIns1-H2b-mCherry (Jax # 028589) and either Sst-Cre (delta) or Gcg-cre (alpha) cells and a floxed YFP allele to label delta or alpha cells, respectively. Islets from replicate groups of 10 to 12 triple transgenic animals for each group were pooled by sex to obtain sufficient material. Pooled islets were dissociated, sorted and collect in Trizol for RNA isolation and library construction.
2016-06-26 | E-GEOD-80673 | biostudies-arrayexpress
Project description:Rodent models are widely used to study diabetes. Yet, significant gaps remain in our understanding of mouse islet physiology that reduce their accuracy as a model for human islet disease. We generated comprehensive transcriptomes of mouse beta and alpha cells using a novel bitransgenic mouse model generated for this purpose. This enables systematic comparison across thousands of genes between the two major endocrine cell types of the islets of Langerhans whose principal hormones are of cardinal importance for glucose homeostasis. Our data leveraged against similar data for human beta cells reveal a core common beta cell transcriptome of 9900+ genes and marked differences in the repertoire of receptors and long non-coding RNAs between mouse and human beta cells. The comprehensive comparison of the (dis)similarities between mouse and human beta cells represents an invaluable resource to boost the effectiveness by which rodent models offer guidance in finding cures for human diabetes. FACS purified alpha and beta cells from the same islets. Islets were isolated from bitransgenic offspring of a cross between mIns1-H2b-mCherry and S100b-eGFP transgenic reporter mice that mark beta and alpha cells, respectively. Islets from two replicate groups of 10 or 11 animals were pooled by sex to obtain sufficient material. Pooled islets were dissociated, sorted and collect in Trizol for RNA isolation and library construction.
2014-09-16 | E-GEOD-54973 | biostudies-arrayexpress
Project description:Rodent models are widely used to study diabetes. Yet, significant gaps remain in our understanding of mouse islet physiology, including the maintenance of mature endocrine cell fate. We generated comprehensive transcriptomes beta cells that transdifferentiated from delta cells using a triple transgenic mouse models generated for this purpose.
2019-12-01 | GSE90767 | GEO
Project description:Rodent models are widely used to study diabetes. Yet, significant gaps remain in our understanding of mouse islet physiology that reduce their accuracy as a model for human islet disease. We generated comprehensive transcriptomes of mouse beta and alpha cells using a novel bitransgenic mouse model generated for this purpose. This enables systematic comparison across thousands of genes between the two major endocrine cell types of the islets of Langerhans whose principal hormones are of cardinal importance for glucose homeostasis. Our data leveraged against similar data for human beta cells reveal a core common beta cell transcriptome of 9900+ genes and marked differences in the repertoire of receptors and long non-coding RNAs between mouse and human beta cells. The comprehensive comparison of the (dis)similarities between mouse and human beta cells represents an invaluable resource to boost the effectiveness by which rodent models offer guidance in finding cures for human diabetes.
2014-09-16 | GSE54973 | GEO
Project description:Rodent models are widely used to study diabetes. Yet, significant gaps remain in our understanding of mouse islet physiology, including the maintenance of mature endocrine cell fate. We generated comprehensive transcriptomes beta cells that transdifferentiated from alpha cells using a triple transgenic mouse models generated for this purpose.
2017-04-04 | GSE90766 | GEO
Project description:Pancreatic islets are essential for maintaining physiological blood glucose levels, and declining islet function is a hallmark of type 2 diabetes. Here we employ mass spectrometry (MS)-based proteomics to systematically analyse purified islets from 9 genetic or diet-induced mouse models representing a broad cross-section of metabolic health. Quantifying the islet proteome to a depth of >11,500 proteins, this study represents the most detailed analysis of islet proteins to date. Our data highlight that the vast majority of islet proteins are expressed in all strains and diets, but more than half of the proteins vary in expression levels. Associating these varied protein expression levels on an individual animal basis with individual phenotypic measures reveals islet mitochondrial function as a major positive indicator of metabolic health. This compendium of strain-specific and dietary changes to mouse islet proteomes represents a comprehensive resource for basic and translational islet cell biology.
2021-10-08 | PXD024522 | Pride
Project description:We have used RNA-seq to identify transcripts, including splice variants, expressed in human islets of Langerhans under control condition or following exposure to the pro-inflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ). A total of 29,776 transcripts were identified as expressed in human islets. Expression of around 20% of these transcripts was modified by pro-inflammatory cytokines, including apoptosis- and inflammation-related genes. Chemokines were among the transcripts most modified by cytokines. Interestingly, 35% of the genes expressed in human islets undergo alternative splicing as annotated in RefSeq, and cytokines caused substantial changes in spliced transcripts. Nova1, previously considered a brain-specific regulator of mRNA splicing, is expressed in islets. 25/41 of the candidate genes for type 1 diabetes are expressed in islets, and cytokines modified expression of several of these transcripts. 5 human islet of Langerhans preparations examined under 2 conditions (control and cytokine treatment)
2012-03-09 | E-GEOD-35296 | biostudies-arrayexpress
Project description:The purpose of this study was to identify mRNA transcripts encoding tissue restricted cell surface proteins on human islet tissue that, in turn, might serve as markers for determination of healthy, transplanted and/or diseased islet cell mass. Using oligonucleotide microarrays and clinical grade human islets, we obtained the gene expression profiles of cultured normal islet tissue and compared them to profiles of islets treated with interferon alpha 2 beta, islet-depleted exocrine pancreas, pooled whole pancreas, pooled liver and pooled kidney tissue. Data set filtering and comparisons of gene expression patterns revealed a small set of genes corresponding to transmembrane or membrane associated proteins with limited tissue distributions (present in Islets of Langerhans and, often, central or peripheral nervous system tissues, but absent from exocrine pancreas, liver, kidney and other tissues) with possible utility as novel islet markers. Under the influence of IFN alpha, some of these transcripts show differential expression as confirmed by real time PCR. In addition, we found significant differential expression of two sets of transcripts expressed in islets but with broad tissue distributions, non classical MHC class I b (HLA-G and F) and MHC Class II locus (e.g. HLA-DR alpha and HLA-DQ alpha and beta).
2007-04-06 | E-CBIL-27 | biostudies-arrayexpress
Project description:Expression of CD40 in non-hematopoietic cells has been linked to inflammation. We presented evidence that CD40, a T-cell costimulatory molecule, is expressed in human β-cells and the engagement of CD40 in insulinoma cells activated the NFKB and ERK1/2 pathways. CD40 activation in human islets cells induced secretion of IL-8, MCP-1 and MIP-1 β, which is abrogated by inhibitors of NFkB and ERK1/2 inhibitors. In this study, we have studied gene expression mediated by CD40-CD40L interaction in islet cells. This approach identified 90 genes and transcripts exhibiting at least a 1.7 fold increase in their expression intensity after treatment with soluble CD40L. A significant number of genes were related to inflammation and oxidative stress. We have a strong overexpression of CXCL1 (Groα), CXCL2 (Mif2) and CXCL3; chemokines belonging to CXC family structurally related to Il-8. 11 genes were selected from this group and further quantified by Real Time PCR, including CXCL1. Activation of islet cells with CD40L induced the secretion of CXCL1 in a NFKB dependent manner. Engagement of CD40 in islet cells did not induce apoptosis, neither β-cell death and did not enhanced TNF-α mediated cell death as observed in insulinoma cells. CD40 activation in insulinoma cells, results in ERK1/2 dependent phsophorylation of synapsin I, a protein associated with the exocytosis machinery in neurons and β-cells. However, treatment of islets with soluble CD40L did not affect glucose induced insulin secretion. It has been reported that ductal cells always present in human islet preparations express CD40 constitutively (ref). We found that CD40-CD40L interaction in ductal cells, unlike in β-cells, induces secretion of diabetogenic cytokines IFNγ and TNF-α. Furthermore, incubation of islets containing ductal cells with CD40L decreased β-cells viability as assessed by measurement of their mitochondrial membrane potential Keywords: Pancreas, Islets of Langerhans, chemokines, cytokines, inflammation, apoptosis, Nuclear Factor-κB(NFκB)
2008-08-01 | GSE8873 | GEO
Project description:Transgenic mice were generated that expressed the inhibitor of apoptosis and mitotic regulator survivin in pancreatic islet beta cells. Control non-transgenic or transgenic islets were then used in a model of islet transplantation in diabetic recipient mice and tested for their ability to correct hyperglycemia and allow long-term engraftment of tranplanted islets in vivo. Control or transgenic islets were analyzed by chip microarray for potential transcriptional changes associated with transgenic expression of survivin, in vivo.
2006-01-16 | E-MEXP-536 | biostudies-arrayexpress