The zinc finger transcription factor growth-factor-independent-1 (Gfi1) has been involved in various cellular differentiation processes. Gfi1 acts as a transcriptional repressor and splicing control factor upon binding to cognate binding sites in regulatory elements of its target genes. Here, we report that Gfi1-deficient mice develop autoimmunity. Gfi1-deficient peripheral B-cells show a hyperproliferative phenotype, leading to expansion of plasma cells, increased levels of nuclear autoantibodies, and immunoglobulin deposition in brain and kidneys. Dysregulation of multiple transcription factors and cell-cycle control elements may contribute to B-cell dependent autoimmunity. Gfi1 thus emerges as a novel master-regulator restricting autoimmunity.
Transcription factor Gfi1 restricts B cell-mediated autoimmunity.
Specimen part
View SamplesEpithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is dynamically expressed in human and murine renal epithelia during development. The levels of EpCAM in the renal epithelium are upregulated both during regeneration after ischemia/reperfusion injury and in renal-derived carcinomas. The role of EpCAM in early kidney development, however, has remained unclear. To identify potential programs and signaling pathways that are controlled by EpCAM during pronephros development, we developed a method to study the transcriptomes of specific pronephric segments. Combining laser capture microdissection (LCM) with RNA sequencing (RNA-seq), we generated genome-wide transcriptional profiles of the distal late tubules of wild type and EpCAM-deficient embryos. Overall design: RNA-seq of LCM-dissected pronephric cells from EpCAM-deficient and control zebrafish embryos
EpCAM controls morphogenetic programs during zebrafish pronephros development.
No sample metadata fields
View SamplesThe molecules RhoC and RhoA are essential factors for invasion/metastasis of tumor cells proliferation, respectively. RhoC over-expression was especially linked to aggressive cancers, which requires loss of epithelial polarity and deregulation of cellular adhesion. This epithelial-mesenchymal transition (EMT) includes a change in gene expression pattern through several transcription factors, like Snail, ZEB1 or Twist. Here we analyze the potential of RhoC to induce EMT, migration and invasion and to regulate specific genes involved in tumorigenesis. We established stable MCF-10A cell lines with RhoA/RhoC expression under the control of a doxycycline-regulated trans-activator and a transcriptional silencer allowing conditional expression of RhoA and RhoC, respectively. We additionally quantified the transcriptional response from two bacterial toxins: Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1) and Yersinia pseudotuberculosis Cytotoxic Necrotizing Factor (CNFY) to directly activate the endogenous pool of Rho GTPases and characterized changes in morphology, migration and invasion upon induction of RhoA/RhoC expression or activation by the toxins in MCF-10A grown in two- and three-dimensions. The transcriptome response identified PTGS2 as RhoC specific target genes involved in pro-migratory changes which was experimentally validated.
Specific role of RhoC in tumor invasion and metastasis.
Cell line
View SamplesWe assessed the usability of microarrays, which base on formalin-fixed paraffin-embedded (FFPE) tissue.
Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.
Specimen part, Disease
View SamplesWe assessed the feasibility and reliability of microarray studies using formalin-fixed paraffin-embedded (FFPE) tissue-derived RNA compared with transcriptome data from paired fresh-frozen (FF) material. We established a robust workflow to generate highly reproducible microarray datasets from only 2 ng RNA input. For prior quality assessment, inspection of Agilent Bioanalyzer electropherograms, calculation of RNA fragment size distribution (DV200) and routine qPCR for selected references genes were done.
Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.
Specimen part
View SamplesAttainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue.
Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.
No sample metadata fields
View SamplesPrevious studies have reported that microglia depletion leads to impairment of synapse formation and these cells rapidly repopulate from CNS progenitors. However, the impact of microglia depletion and repopulation on the long-term state of the CNS environment has not been characterized. Here, we found by RNA-seq analysis that acute and synchronous microglia depletion results in a type 1-interferon inflammatory signature in degenerating somatosensory cortex in microglia-depleted mice. Transcriptomic and mass cytometry analysis of repopulated microglia demonstrates an interferon regulatory factor 7-driven activation state. Minocycline and anti-IFNAR1 antibody treatment attenuate the CNS type-1 interferon-driven inflammation and restore microglia homeostasis. Together, we found that acute microglia ablation induces a type-1 interferon activation state of grey matter microglia associated with acute neurodegeneration. Overall design: RNAseq analysis of brain cortical tissue from control and microglia-depleted mice.
Acute microglia ablation induces neurodegeneration in the somatosensory system.
Specimen part, Subject
View SamplesTranscriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis
Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
Specimen part
View SamplesTranscriptome analyses of normal gingival fibroblasts after knockdown of DLX5 and RUNX2 long forms.
Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.
Specimen part
View Samples