Filters
Organism
Technology
Platform
GSE43581
Mus musculus
12 Downloadable Samples
Description
We assessed the impact of glucose transporter Glut2 gene inactivation in adult mouse liver (LG2KO mice). This suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was normal early after Glut2 inactivation but intolerance developed at later time. This was caused by progressive impairment of glucose-stimulated insulin secretion even though beta-cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinate down-regulation of cholesterol biosynthesis genes in LG2KO mice. This was associated with reduced hepatic cholesterol in fasted mice and a 30 percent reduction in bile acid production. We showed that chronic bile acids or FXR agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from fxr-/- mice. Collectively, our data show that glucose sensing by the liver controls beta-cell glucose competence, through a mechanism that likely depends on bile acid production and action on beta-cells.
Publication Title
Hepatic glucose sensing is required to preserve β cell glucose competence.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 40 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 40 Downloadable Samples
Description
We used microarrays to detail the global programme of gene expression in response to Influenza A (PR8) infection
Publication Title
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
Description
The vertebrate retina uses diverse neuronal cell types arrayed into complex neural circuits to extract, process and relay information from the visual scene to the higher order processing centers of the brain. Amacrine cells, a diverse class of inhibitory interneurons, are thought to mediate the majority of the processing of the visual signal that occurs within the retina. Despite morphological characterization, the number of known molecular markers of amacrine cell types is still much smaller than the 26 morphological types that have been identified. Furthermore, it is not known how this diversity arises during development. Here, we have combined in vivo genetic labeling and single cell genome-wide expression profiling to: 1) Identify specific molecular types of amacrine cells; 2) Demonstrate the molecular diversity of the amacrine cell class.
Publication Title
Development and diversification of retinal amacrine interneurons at single cell resolution.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 2 Downloadable Samples
Description
The goal of the project was to isolate single miRNA-expressing cells labelled by GFP reporter genes under the control of endogenous miRNA promoters and analyze expression levels of miRNA target genes in these cells. GFP-positive miRNA-expressing cells and GFP-negative cells from the rest of the embryos were purified at the same developmental stage to the cellular resolution using fluorescent activated cell sorting (FACS). Focus was on regulation by miR-206 and miR-133 in the developing somites and miR-124 in the developing central nervous system. Comparison of wild-type embryos and those lacking miRNAs revealed predicted
Publication Title
Coherent but overlapping expression of microRNAs and their targets during vertebrate development.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Scaffold proteins regulate intracellular MAP kinase signaling by providing critical spatial and temporal specificity. We have shown previously that the scaffold protein MEK1 partner (MP1) is localized to late endosomes by the adaptor protein p14. Using conditional gene disruption of p14 in livers of mice we analysed protein and transcript signatures in tissue samples. Further biological network analysis predicted that the differentially expressed transcripts and proteins are involved in cell cycle progression and regulation of cellular proliferation. Although some of the here identified signatures were previously linked to phospho-ERK activity, most of them were novel targets of late endosomal p14/MP1/MEK/ERK signaling module. Finally, the proliferation defect was confirmed in a chemically induced liver regeneration model in p14 liver knock-out mice.
Publication Title
Comprehensive proteomic and transcriptomic characterization of hepatic expression signatures affected in p14 liver conditional knockout mice.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Description
Continuous regeneration of digestive enzyme (zymogen) secreting chief cells is a normal aspect of stomach function that is disrupted in pre-cancerous lesions. Regulation of zymogenic cell (ZC) differentiation is poorly understood. Here we profile Parietal, Pit, and Zymogenic cells for comparison and study.
Publication Title
The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 51 Downloadable Samples
Description
The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin- Sca1+ c-kit+) stem cells while committed granulocyte-monocyte progenitors (GMPs) were transformation-resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll- AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 up-regulated expression of 196 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors.
Publication Title
Malignant transformation initiated by Mll-AF9: gene dosage and critical target cells.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 26 Downloadable Samples
Description
Gene expression profiling of newborn lung tissue revealed few changes in compound FGFR3/FGFR4 deficient mice, consistent with their normal lung morphology at birth, suggesting the sequence of events leading to the phenotype initiates after birth in this model.
Publication Title
Fibroblast growth factor receptors control epithelial-mesenchymal interactions necessary for alveolar elastogenesis.
Alternate Accession IDs
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Variant late-infantile (vLINCL) and juvenile neuronal ceroid lipofuscinosis (JNCL) share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and vLINCL CbCln6nclf cerebellar cells and compared them to wild-type and JNCL CbCln3ex7/8 cerebellar cells. CbCln6nclf/nclf cells and CbCln3ex7/8/ex7/8 cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6nclf/nclf cells, while fluid-phase endocytosis and LysoTracker labeled vesicles were decreased in both CbCln6nclf/nclf and CbCln3ex7/8/ex7/8 cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3ex7/8 and Cln6nclf mutations. Thus, these data support the hypothesis that vLINCL and JNCL mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival.
Publication Title
Distinct early molecular responses to mutations causing vLINCL and JNCL presage ATP synthase subunit C accumulation in cerebellar cells.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples