Cultured epidermal keratinocytes treated with OsM 1, 4, 24 & 48hrs, and Skinethic epidermal substitutes treated 1, 4, 24, 48h & 7days, each with untreated control
Transcriptional responses of human epidermal keratinocytes to Oncostatin-M.
No sample metadata fields
View SamplesMLLT10, a 24 exons gene at 10p12, is known in leukemogenesis as partner of MLL or PICALM and recently NAP1L1. We identified HNRNPH1 and DDX3X, genes involved in RNA processing, as new MLLT10 partners in 2 cases of pediatric NOTCH1 positive T-ALL. HNRNPH1/5q35 encodes for a member of the ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) subfamily of RNA binding protein. DDX3X/Xp11.3, belongs to the big family of RNA helicases with a DEAD box domain.
New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia.
Disease
View SamplesWe have cloned and characterized a fusion gene NUP98/HHEX1 resulting from t(7;10) from a patient with acute myeloid leukemia (AML). As NUP98/HHEX acts as an aberrant transcriptional activator, putative targets were searched upon transient expression of the fusion in primary murine bone marrow cells.
Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia.
No sample metadata fields
View SamplesGEP class prediction in association with CI-FISH (42 candidate genes) and patient MRD stratification
Linking genomic lesions with minimal residual disease improves prognostic stratification in children with T-cell acute lymphoblastic leukaemia.
Specimen part, Disease, Disease stage
View SamplesSexual selection involves mate preference behavior and is a critical determinant for natural selection and evolutionary biology. Previously an environmental compound (fungicide vinclozolin) was found to promote epigenetic transgenerational inheritance of modified mate selection characteristics in all progeny for three generations after exposure of a gestating female. The current study investigated gene networks involved in various regions of the brain that correlated with the mate preference behavior altered in F3-Vinclozolin lineage animals. Statistically significant correlations of differentially expressed gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified critical gene networks involved in mate preference behavior and demonstrated the ability of environmental factors to promote epigenetic transgenerational inheritance of this altered evolutionary biology determinant. Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology.
Gene bionetworks involved in the epigenetic transgenerational inheritance of altered mate preference: environmental epigenetics and evolutionary biology.
Sex, Age, Specimen part
View SamplesEmbryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.
Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.
No sample metadata fields
View SamplesIn this experiment, total RNA was extracted from asynchronous population of L1210 cells and hybridized to Affymetrix 430A 2.0 arrays in order to obtain an expression profile of these cells. We have previously mapped the replication timing of the entire mouse genome in this cell line, using mouse CGH arrays (see E-MEXP-1022). We wanted to validate in our system the known correlation between early replication and expression and to analyze its extent. To this end, we have measured the expression in the same cell line (L1210 cells). Two biological replicates were hybridized to 2 identical microarrays. Expression levels were highly similar between the 2 replicates (r=0.98).
Global organization of replication time zones of the mouse genome.
Cell line, Subject
View SamplesBackground and aims: Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. Incidence is increasing worldwide and these cancers collectively represent the second most common primary liver tumour. CCAs are characterized by genetic and epigenetic alterations that determine their pathogenesis. Hypermethylation of the SOX17 promoter was recently reported in human CCA tumours. SOX17 seems to be a key transcription factor for biliary embryogenesis. Here, we evaluated the role of SOX17 in cholangiocyte differentiation and in cholangiocarcinogenesis. Methods: SOX17 expression and function was evaluated during the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation of normal human cholangiocytes (NHC) and in cholangiocarcinogenesis. Lentiviruses overexpressing or knocking-down SOX17 (Lent-SOX17 and Lent-shRNA-SOX17, respectively) were used. Gene expression arrays were performed. Results: SOX17 expression is highly induced in the later stages of cholangiocyte differentiation from iPSC, and mediates the acquisition of the biliary markers cytokeratin (CK) 7 and 19, as well as fibronectin. In addition, SOX17 becomes progressively downregulated in NHC over serial cell passages in vitro and this event is associated with cellular senescence; however, experimental SOX17 knocking-down in differentiated NHC decreased the expression of both CK7 and 19 without affecting cellular senescence. SOX17 expression is reduced in CCA cells compared to NHC, as well as in human CCA tissue compared to human gallbladder tissue or NHC. In a murine xenograft model, overexpression of SOX17 in CCA cells decreased their tumorigenic capacity related to increased oxidative stress and apoptosis. Interestingly, overexpression of SOX17 in NHC did not affect their survival. Moreover, SOX17 overexpression inhibited the Wnt/-catenin-dependent proliferation in CCA cells and was associated with upregulation of biliary epithelial markers and restoration of the primary cilium length. Both Wnt3a and TGF1 decreased SOX17 expression in NHC in a DNMT1-dependent manner. Inhibition of DNMT1 in CCA cells with siRNAs or pharmacological drugs upregulated SOX17 expression. Conclusion: SOX17 regulates the cholangiocyte phenotype and becomes epigenetically downregulated in CCA. SOX17 acts as a tumour suppressor in CCA, and restoration of its expression may have important therapeutic value.
SOX17 regulates cholangiocyte differentiation and acts as a tumor suppressor in cholangiocarcinoma.
Specimen part, Treatment
View SamplesEpigenetic changes are crucial for the generation of immunological memory1-4. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing immune memory. Yet the transcription factors that regulate these processes are poorly defined, as are the chromatin modifying complexes they recruit and the chromatin modifications they control. Using pathogen infection models and three different mouse models, including a new conditional allele, we find that the widely expressed transcription factor Oct15, and its cofactor OCA-B6,7, are selectively required the in vivo generation of functional CD4 memory. In vitro, both proteins are also required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4 T cells, and to generate robust Il2 expression upon restimulation. OCA-B is also required for the robust re-expression of other known targets including Il17a, and Ifng. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a8 to targets such as Il2 and Ifng. The findings pinpoint Oct1 and OCA-B as unanticipated mediators of CD4 T cell memory. Overall design: Examination of 4 different conditions in 2 genotypes
Oct1 and OCA-B are selectively required for CD4 memory T cell function.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling.
Cell line, Treatment, Time
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