Comprehensive transcriptomes of mouse pancreatic beta cells that transdifferentiated from alpha cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE90766 | GEO | 2017/04/04
SECONDARY ACCESSION(S): PRJNA355870
REPOSITORIES: GEO
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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. 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.
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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 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. 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.
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Project description:During pancreas development, endocrine progenitors differentiate into the islet-cell subtypes, which undergo further functional maturation in postnatal islet development. In islet b-cells, genes involved in glucose-stimulated insulin secretion are activated and glucose exposure increases the insulin response as b-cells mature. Here, we investigated the role of H3K4 trimethylation in endocrine cell differentiation and functional maturation by disrupting TrxG complex histone methyltransferase activity in mouse endocrine progenitors. In the embryo, genetic inactivation of TrxG component Dpy30 in NEUROG3+ cells did not affect the number of endocrine progenitors or endocrine cell differentiation. H3K4 trimethylation was progressively lost in postnatal islets and the mice displayed elevated non-fasting and fasting glycemia, as well as impaired glucose tolerance by postnatal day 24. Although postnatal endocrine cell proportions were equivalent to controls, islet RNA-sequencing revealed a downregulation of genes involved in glucose-stimulated insulin secretion and an upregulation of immature b-cell genes. Comparison of histone modification enrichment profiles in NEUROG3+ endocrine progenitors and mature islets suggested that genes downregulated by loss of H3K4 trimethylation more frequently acquire active histone modifications during maturation. Taken together, these findings suggest that H3K4 trimethylation is required for the activation of genes involved in the functional maturation of pancreatic islet endocrine cells.
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Project description:Mouse pancreatic islet scRNA-seq integrated atlas encompassing different ages, sexes, chemical stress leading to dedifferentiation, and diabetes models with corresponding treatments. Two datasets (sub-series) were newly generated for the atlas.
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Project description:In the past decade, several transcription factors critical for pancreas development have been identified. Despite this success, many of the cell surface and extracellular factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor HNF6 specifically in the pancreatic endocrine cell lineage resulted in the disruption of islet morphogenesis, including dysfunctional endocrine cell sorting, increased islet size, and failure of islets to migrate away from the ductal epithelium. We exploited the dysmorphic islets in pdx1PBHnf6 animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal pancreas tissue from wild type and pdx1PBHnf6 animals. We report the identification of genes with an altered expression in HNF6 Tg animals and highlight factors with potential importance in islet morphogenesis. Experiment Overall Design: Whole genome microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal pancreas tissue from wild type (WT) animals and HNF6 transgenic animals at a time when the events of normal islet morphogenesis are occurring (e18.5 and postnatal day 1). RNA was isolated from individual pancreata at the appropriate developmental stage. Highly pure samples were pooled according to their genotype (3-5 animals per pool) in order to obtain an adequate quantity of RNA for Affymetrix GeneChip analysis. Twelve samples were run in total, 3 replicates each of 4 groups: embryonic day 18.5, wild type mouse; embryonic day 18.5, HNF6 Transgenic mouse; post-natal day 1, wild type mouse; post-natal day 1, HNF6 Transgenic mouse.
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