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GSE18224
Mus musculus
32 Downloadable Samples
Description
Aims: We investigate sex differences and the role of oestrogen receptor beta (ERbeta) in a mouse model of pressure overload-induced myocardial hypertrophy. Methods and results: We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERbeta knockout (ERbeta-/-) C57Bl6 mice. All mice were characterised by echocardiography and haemodynamic measurements and were sacrificed nine weeks after surgery. Left ventricular (LV) samples were analysed by microarray profiling, real-time RT-PCR and histology. After nine weeks, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. These sex differences were abolished in ERbeta-/- mice. ERbeta deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that male WT hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than female hearts. ERbeta-/- mice exhibited a different transcriptome. Induction of pro-apoptotic genes after TAC occurred in ERbeta-/- mice of both sexes with a stronger expression in ERbeta-/- males. Histological analysis revealed, that cardiac fibrosis was more pronounced in male WT TAC than in female mice. This was abolished in ERbeta-/- mice. Apoptosis was significantly induced in both sexes of ERbeta-/- TAC mice, but it was most prominent in males. Conclusion: Female sex offers protection against ventricular chamber dilation in the TAC model. Both the female sex and ERbeta attenuate the development of fibrosis and apoptosis; thus slowing the progression to heart failure.
Publication Title
Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload.
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Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
A soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet.
Publication Title
Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
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Sample Metadata Fields
Sex, 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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Specimen part
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