Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown.
Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated microRNA and mRNA Signature Associated with the Transition from the Locally Confined to the Metastasized Clear Cell Renal Cell Carcinoma Exemplified by miR-146-5p.
Sex, Age, Specimen part
View SamplesTo investigate the mechanisms of ccRCC progression and metastasis, we performed expression profiling of human kidney cancer and benign tissues.
Integrated microRNA and mRNA Signature Associated with the Transition from the Locally Confined to the Metastasized Clear Cell Renal Cell Carcinoma Exemplified by miR-146-5p.
Sex, Age, Specimen part
View SamplesTo investigate the mechanisms of kidney tumor progression and metastasis, we performed expression profiling of human kidney cancer and benign tissues.
Integrated microRNA and mRNA Signature Associated with the Transition from the Locally Confined to the Metastasized Clear Cell Renal Cell Carcinoma Exemplified by miR-146-5p.
Sex, Age, Specimen part
View SamplesAlveolar macrophages orchestrate pulmonary innate immunity and are essential for early immune surveillance and clearance of microorganisms in the airways. Inflammatory signaling must be sufficiently robust to promote host defense but limited enough to prevent excessive tissue injury. Macrophages in the lungs utilize multiple transcriptional and post-transcriptional mechanisms of inflammatory gene expression to delicately balance the elaboration of immune mediators. RNA terminal uridyltransferases (TUTs), including the closely homologous family members Zcchc6 (TUT7) and Zcchc11 (TUT4), have been implicated in the post-transcriptional regulation of inflammation from studies conducted in vitro. In vivo, we observed that Zcchc6 is expressed in mouse and human primary macrophages. Zcchc6-deficient mice are viable and born in Mendelian ratios and do not exhibit an observable spontaneous phenotype under basal conditions. Following an intratracheal challenge with S. pneumoniae, Zcchc6 deficiency led to a modest but significant increase in the expression of select cytokines including IL-6, CXCL1, and CXCL5. These findings were recapitulated in vitro whereby Zcchc6-deficient macrophages exhibited similar increases in cytokine expression due to bacterial stimulation. Although loss of Zcchc6 also led to increased neutrophil emigration to the airways during pneumonia, these responses were not sufficient to impact host defense against infection.
The RNA uridyltransferase Zcchc6 is expressed in macrophages and impacts innate immune responses.
No sample metadata fields
View SamplesIn the adult mouse, distinct morphological and transcriptional differences separate stomach from intestinal epithelium. Remarkably, the epithelial boundary between these two organs is literally one cell thick. This discrete junction is established suddenly and precisely at embryonic day (E) 16.5, by sharpening a previously diffuse intermediate zone. In the present study, we define the dynamic transcriptome of stomach, pylorus and intestinal tissues between E14.5 and E16.5. We show that establishment of this boundary is concomitant with the induction of over a thousand genes in intestinal epithelium, and these gene products provide intestinal character. Hence, we call this process intestinalization. We identify specific transcription factors (Hnf4g, Creb3l3 and Tcfec) and examine signaling pathways (Hedgehog and Wnt) that may play a role in this process. Finally, we define a unique expression domain at the pylorus itself and detect novel pylorus-specific patterns for the transcription factor Gata3 and the secreted protein nephrocan.
Dynamic patterning at the pylorus: formation of an epithelial intestine-stomach boundary in late fetal life.
Specimen part
View SamplesWe used microarrays to detail the program of gene expression underlying the growth of the plantaris muscle following synergist ablation-induced supraphysiological overload
Changes in muscle fiber contractility and extracellular matrix production during skeletal muscle hypertrophy.
Specimen part
View SamplesBackground: The muscularis externa (ME) of the adult intestine consists of two layers of visceral smooth muscle (VISM), the inner circular muscle (ICM) and outer longitudinal muscle (OLM), that form sequentially beginning at embryonic day (E) 13 and E15 in the developing mouse. Coordinated contraction of these two layers facilitates the movement of food down the digestive tract. Though abnormal ME function or development has been linked to pseudoobstruction and irritable bowel syndrome, little is known about the molecular character of the smooth muscle that comprises this tissue. We performed transcriptome analysis to identify genes that are enriched in intestinal mesenchyme tissue at E14.5, when the inner circular muscle (ICM) is well established. Results: Expression patterns of enriched mesenchyme genes were examined in publically available in situ databases, revealing over one hundred genes that are expressed in the ICM. Examination of the promoter regions for these genes revealed enrichment for cJUN transcription factor binding sites and cJUN itself was also enriched in ICM. A cJUN ChIP-seq at E14.5 showed that cJUN regulatory regions contained characteristics of muscle enhancers. Overall design: E14.5 mouse intestines were harvested and grown for 24 hours in a transwell culture with or without Cyclopamine treatment. Separated epithelial and mesenchyme tissue populations or whole intestines were submitted for sequencing. Three replicates for each condition were collected.
Transcriptome of the inner circular smooth muscle of the developing mouse intestine: Evidence for regulation of visceral smooth muscle genes by the hedgehog target gene, cJun.
Specimen part, Cell line, Subject
View SamplesDuring organogenesis of the intestine, reciprocal crosstalk between the endodermally-derived epithelium and the underlying mesenchyme is required for regional patterning and proper differentiation. Though both of these tissue layers participate in patterning, the mesenchyme is thought to play a prominant role in the determination of epithelial phenotype during development and in adult life. However, the molecular basis of this instructional dominance is unclear. In fact, surprisingly little is known about the cellular origins of many of the critical signaling molecules and the gene transcriptional events that they impact. Here, we profile genes that are expressed in separated mesenchymal and epithelial compartments of the perinatal mouse intestine. The data indicate that the vast majority of soluble modulators of signaling pathways such as Hedgehog, Bmp, Wnt, Fgf and Igf are expressed predominantly or exclusively by the mesenchyme, accounting for its ability to dominate instructional crosstalk. We also catalog the most highly enriched transcription factors in both compartments and find evidence for a major role for Hnf4alpha and Hnf4 gamma in the regulation of epithelial genes. Finally, we find that while epithelially enriched genes tend to be highly tissue-restricted in their expression, mesenchymally-enriched genes tend to be broadly expressed in multiple tissues. Thus, the unique tissue-specific signature that characterizes the intestinal epithelium is instructed and supported by a mesenchyme that itself expresses genes that are largely non-tissue specific.
Deconvoluting the intestine: molecular evidence for a major role of the mesenchyme in the modulation of signaling cross talk.
No sample metadata fields
View SamplesEpithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme.
Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria.
Specimen part
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