Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.
Sex, Age
View SamplesWe investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans. Male Wistar Kyoto (WKY) and Sprague Dawley (SD) rats were dosed once with 1, 2.5 and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days.
Glomerulonephritis-Induced Changes in Urinary and Kidney MicroRNA Profiles in Rats.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity.
Specimen part, Cell line
View SamplesTGF-b1-stimulation induces an epithelial dedifferentiation-process, throughout which epithelial cell sheets disintegrate and gradually switch into fibroblastic-appearing cells (EMT-like transition). The purpose of these profiles was to identify differentially expressed genes that are regulated transcriptionally. Standard microarry-based gene expression profiles measure steady-state RNA but do not provide insight into underlying regulatory principles. NIAC-NTR-based gene expression profiling (Kenzelmann et al., PNAS, 2007) essentially enables the dissection of transcriptionally versus non-transcriptionally regulated genes within respective analysed time-frames. Briefly, NIAC-NTR relies on incorporation of 4sU (thio-uridine) into nascent RNA, which can subsequently be specifically isolated by custom-made columns. Total- and enriched (4sU-labeled) are then further processed for microarray gene expression profiling by standard procedures. This dataset complements previously released data of NIAC-NTR-based gene expression profiling of cells treated with TGF-b1 and 4sU for 2hrs [GSE23833].
Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity.
Specimen part, Cell line
View SamplesTGF-b1-stimulation induces an epithelial dedifferentiation-process, throughout which epithelial cell sheets disintegrate and gradually switch into fibroblastic-appearing cells (EMT-like transition). Several transcription factors, some of them being TGF-b1-responsive, are functionally involved in such a switch and affect epithelial differentiation and plasticity.
Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity.
Specimen part, Cell line
View SamplesThe goal of the experiment was to assay the role of the glucocorticoid receptor (GR) in development of mesenchynmal cells of the lung occuring between the 16 and 18 day of embryonal development.
Glucocorticoid activity during lung maturation is essential in mesenchymal and less in alveolar epithelial cells.
Specimen part
View SamplesThe Forkhead family of transcription factors comprises numerous members and is implicated in various cellular functions, including cell growth, apoptosis, migration and differentiation.In this study we identified the Forkhead factor FoxQ1 as increased in expression during TGF-beta1 induced changes in epithelial differentiation, suggesting functional roles of FoxQ1 for epithelial plasticity.The repression of FoxQ1 in mammary epithelial cells led to a change in cell morphology characterized by an increase in cell size, pronounced cell-cell contacts and an increased expression of several junction proteins (e.g. E-cadherin). In addition, FoxQ1 knock-down cells revealed rearrangements in the actin-cytoskeleton and slowed down cell cycle G1-phase progression.Furthermore, repression of FoxQ1 enhanced the migratory capacity of coherent mammary epithelial cells.Gene expression profiling of NM18 cells indicated that FoxQ1 is a relevant downstream mediator of TGF-beta1 induced gene expression changes. This included the differential expression of transcription factors involved in epithelial plasticity, e.g. Ets-1, Zeb1 and Zeb2.In summary, this study has elucidated the functional impact of FoxQ1 on epithelial differentiation
The Forkhead factor FoxQ1 influences epithelial differentiation.
Specimen part, Treatment
View SamplesSerum response factor (SRF), a MADS-box transcription factor, is essential for murine embryonic development and for the function of muscle cells and neurons. SRF and its transcriptional co-factors are broadly expressed. To determine the in vivo role of SRF in developing lymphocytes we specifically inactivated the murine Srf gene during T or B cell development using lymphocyte-specific Cre transgenic mouse lines. T cell-specific Srf deletion led to a severe block in thymocyte development at the transition from double to single positive stage. The few residual T cells detectable in the periphery retained at least one functional Srf allele, thereby demonstrating the importance of SRF in T cell development. In contrast, deletion of Srf in developing B cells did not interfere with the growth and survival of B cells in general, yet led to a complete loss of marginal zone B cells and a marked reduction of the CD5+ B cell subset. Our study also revealed a contribution of SRF to the expression of the surface molecules IgM, CD19, and the chemokine receptor 4 in B lymphocytes.
Serum response factor contributes selectively to lymphocyte development.
Specimen part
View SamplesDifferentiation of epithelial cells is strongly affected by transcription factors related to epithelial to mesenchymal-like progression.
Zeb1 affects epithelial cell adhesion by diverting glycosphingolipid metabolism.
Specimen part, Cell line
View SamplesTamoxifen-induced deletion of endogenous GlcCer-synthesizing enzyme UDP-glucose:ceramide glucosyltransferase (UGCG) in keratin K14-positive cells results in epidermal GlcCer depletion. We used microarrays to investigate the molecular consequences of Ugcg-depleted mouse epidermis.
Differentiation of epidermal keratinocytes is dependent on glucosylceramide:ceramide processing.
Specimen part
View Samples