RNA-Seq analysis of mouse small intestine enteroendocrine cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE61250 | GEO | 2015/01/01
SECONDARY ACCESSION(S): PRJNA260599
REPOSITORIES: GEO
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Project description:We generated knock-in mice expressing GFP under the control of the endogenous GIP (Glucose-dependent Insulinotropic Polypeptide) promoter that enable the isolation of a purified population of small intestine K cells. Using RNA-Seq, we comprehensively characterized the transcriptomes of GIP-GFP cells as well as the entire enteroendocrine lineage derived from Neurogenin3 (Ngn3)-expressing progenitors. We interrogated the whole transcriptome of FACS-isolated small intestine GIPGFP cells using high-throughput mRNA sequencing. We also obtained the global gene expression patterns of the entire enteroendocrine cell lineage as well as the non-enteroendocrine cell population, comprising enterocytes, goblet cells and Paneth cells. To achieve this, small intestine epithelial cells from male mice resulting from the breeding of Neurogenin3 (Ngn3)-Cre mice with ROSA26-LoxP-STOP-LoxP-tomato indicator mice were isolated based on Tomato fluorescence and negative staining for CD45. Due to the small cell numbers, we constructed each of the three RNA-Seq libraries (GIPGFP, Ngn3TOMATO, and Ngn3-) using a pool of equal amounts of individual RNA samples without RNA amplification.
2015-01-01 | E-GEOD-61250 | biostudies-arrayexpress
Project description:HNF4A is a transcription factor that controls metabolic features of several endodermal epithelia. Using an intestinal conditional mouse model, here we demonstrate that HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole body energy expenditure under diet-induced obesity (DIO). Deletion of intestinal HNF4A causes mice to become DIO-resistant with preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while reintroduction of a stabilized GIP analog rescues the DIO-resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole body lipid homeostasis and points to a novel non-cell-autonomous regulatory circuit for body fat management.
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Project description:In this study, we assessed nutrient-dependent organ morphogenesis in Xenopus laevis. We performed the RNA-seq analysis of the gastrointestinal (GI) tract for both fed and unfed tadpoles to identify feeding-dependent inter-organ transmitters secreted from GI tract post-prandially during development. We found that one of the GI hormones, glucose-dependent insulinotropic polypeptide (GIP), is required for thyroid morphogenesis.
2022-01-24 | GSE194146 | GEO
Project description:Ambiguity regarding the role of glucose-dependent insulinotropic polypeptide (GIP) in obesity arises from conflicting reports asserting that both GIP receptor (GIPR) agonism and antagonism are effective strategies for inhibiting weight gain. To enable identification and manipulation of Gipr-expressing (Gipr) cells we created GIPR-Cre knock-in mice. As GIPR-agonists have recently been reported to suppress food intake we aimed to identify central mediators of this effect. Gipr cells were identified in the arcuate, dorsomedial, and paraventricular nuclei of the hypothalamus, as confirmed by RNAscope in mouse and human. Single cell RNAseq identified clusters of hypothalamic Gipr cells exhibiting transcriptomic signatures for mural, glial and neuronal cells, the latter expressing somatostatin, but little proopiomelanocortin or agouti-related peptide. Activation of Gq-DREADDs in hypothalamic Gipr cells suppressed food intake in vivo, which was not obviously additive with concomitant GLP1R activation. These data identify hypothalamic GIPR as a target for the regulation of energy balance.
2019-07-24 | GSE134726 | GEO
Project description:Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to exert insulin-independent effects on lipid and bone metabolism. We investigated the effect of a 6-day s.c. GIP infusion on circulating lipids, white adipose tissue (WAT), brown adipose tissue (BAT), hepatic fat content, and inflammatory markers in patients with type 1 diabetes. In a randomized, placebo-controlled, double-blind, crossover study, 20 men with type 1 diabetes underwent a 6-day continuous s.c. infusion with GIP (6 pmol/kg/min) and placebo (saline), with an interposed seven-day washout period. Each intervention period involved three study days: Day 0 (baseline measurements, a baseline abdominal adipose tissue biopsy and blood sampling), Day 1 (fasting blood sample after 24 hours infusion), and Day 6 (fasting blood sample, an abdominal adipose tissue biopsy).
2022-11-08 | PXD034803 | Pride
Project description:High intakes of carbohydrates, particularly sucrose, in Western societies are associated with the development of non-alcoholic fatty liver (NAFL) and diabetes mellitus. It is unclear whether this is related to the carbohydrate quantity or the hormonal responses, particularly Glucose-dependent Insulinotropic Polypeptide (GIP) which is released in the proximal intestine. We, therefore, used the glucose-fructose dimer as proximally resorbed, 1,4-linked sucrose or distally resorbed 1,6-linked palatinose. Palatinose compared to sucrose, indeed, resulted in slower glucose absorption and reduced postprandial insulin and GIP levels. After 22 weeks of isocaloric diets, palatinose feeding prevented hepatic steatosis (48.5%) compared to sucrose and improved glucose tolerance, without differences in body composition and food intake. Ablation of GIP receptor (GIPR) signaling in Gipr-/- mice completely prevented the deleterious metabolic effects of sucrose feeding. Furthermore, our microarray analysis indicated that sucrose increased the hepatic expression of Suppressor of Cytokine Signaling 2 (SOCS2), which is involved in the growth hormone signaling pathway and participates in the development of NAFL. Our results suggest that the site of glucose absorption and the GIP response determine liver fat accumulation and insulin resistance. GIP may play a role in sucrose induced fatty liver by regulating the expression of SOCS2. Expression data from liver tissue of mice fed with isocaloric diets containing either sucrose or palatinose
2014-12-05 | E-GEOD-54723 | biostudies-arrayexpress
Project description:Gene expression profiles of Ngn3-overexpressing cultured hippocampal neurons was compared to the profile of the corresponding control populations. (neurons expressing GFP). Neurogenin3, a proneural transcription factor controlled by Notch receptor, is involved in hippocampal neuron differentiation and synapses, but little is known about the molecular bases of Ngn3 activity in neurons. Microarray analysis indicated that overexpression of Ngn3 upregulated a number of genes related with cytoskeleton dynamics. One of then was Fmn1 whose protein is associated with actin and microtubule cytoskeleton. Overexpression of the isoform Fmn1-Ib in cultured hippocampal neurons induced an increase in the number of primary dendrites and in the number of glutamatergic synaptic inputs without affecting GABAergic synapses resulting in a modification in the balance between excitation and inhibition. The same changes were provoked by overexpression of Ngn3. In addition downregulation of Fmn1 by the use of Fmn1-siRNAs impaired such morphological and synaptic changes induced by Ngn3 overexpression in neurons. These results reveal a previously unknown involvement of Formin1 in dendritic and synaptic plasticity as a key protein in the Nng3 signaling pathway that contributes to understanding of molecular mechanisms of the neuronal differentiation. Cultured hippocampal neurons were transduced using Sindbis virus bearing myc-tagged Ngn3 or GFP as control. Cells were lysed and total RNA was extracted.Gene expression profiles were obtained for each sample and compared
2011-01-27 | E-GEOD-26911 | biostudies-arrayexpress
Project description:The basic helix-loop-helix transcription factor Neurogenin3 (Ngn3/Neurog3) is expressed in endocrine progenitor cells in the embryonic mouse pancreas. Ngn3 controls endocrine cell fate decisions. Ngn3 deficient mice do not develop any pancreatic endocrine cells, including insulin producing beta cells, and die postnatally from diabetes. Therefore, the characterization of gene expression in Ngn3-expressing cells and their progeny is of particular interest for the development of novel strategies for cell replacement therapies in type-1 diabetes. Here we describe two studies. In the first study (8 assays) we used mice where the EYFP (Enhanced Yellow fluorescent Protein) is expressed under the control of Ngn3 regulatory elements (knock add on strategy). EYFP-positive, Ngn3-expressing cells, were FACS sorted from embryonic pancreas at day 15.5 (E15.5), as well as EYFP-negative cells. In the second study (6 assays) we compared wild-type and Ngn3 mutant pancreas at E15.5. All samples were hybridized to Affymetrix GeneChip Mouse Genome 430.2.0 array.
2009-12-03 | E-CBIL-48 | biostudies-arrayexpress
Project description:Gene expression profiles of Ngn3-overexpressing cultured hippocampal neurons was compared to the profile of the corresponding control populations. (neurons expressing GFP). Neurogenin3, a proneural transcription factor controlled by Notch receptor, is involved in hippocampal neuron differentiation and synapses, but little is known about the molecular bases of Ngn3 activity in neurons. Microarray analysis indicated that overexpression of Ngn3 upregulated a number of genes related with cytoskeleton dynamics. One of then was Fmn1 whose protein is associated with actin and microtubule cytoskeleton. Overexpression of the isoform Fmn1-Ib in cultured hippocampal neurons induced an increase in the number of primary dendrites and in the number of glutamatergic synaptic inputs without affecting GABAergic synapses resulting in a modification in the balance between excitation and inhibition. The same changes were provoked by overexpression of Ngn3. In addition downregulation of Fmn1 by the use of Fmn1-siRNAs impaired such morphological and synaptic changes induced by Ngn3 overexpression in neurons. These results reveal a previously unknown involvement of Formin1 in dendritic and synaptic plasticity as a key protein in the Nng3 signaling pathway that contributes to understanding of molecular mechanisms of the neuronal differentiation.
2011-01-27 | GSE26911 | GEO
Project description:The proneural transcription factor Neurogenin3 (Ngn3) plays a critical role in pancreatic endocrine cell differentiation. While previous studies have focused on Ngn3 gene function, little is known about the regulation of Ngn3 protein. Here we demonstrate that Ngn3 protein undergoes cyclin-dependent kinase (cdk)-mediated phosphorylation on multiple serine-proline sites. Replacing wild-type protein with a phosphomutant form of Ngn3 increases α-cell generation, the earliest endocrine cell type to be formed in developing pancreas. Mechanistically, preventing multi-site phosphorylation enhances Ngn3 stability and DNA binding, and promotes the expression of target genes that drive differentiation. In addition to perturbing embryonic endocrine differentiation, un(der)phosphorylated Ngn3 contributes to maintaining adult β-cell differentiation in the presence of pro-proliferation cue. Here we perform transcriptomic analysis of a low number of pancreatic organoid cells expressing wild type and phosphomutant Ngn3. Analysis of the endocrine differentiation programme activated by Ngn3 in this context revealed the cell fate plasticity of the system and demonstrated that preventing Ngn3 phosphorylation enhances endocrine gene expression.
2017-06-09 | GSE96707 | GEO