Alterations to corticostriatal glutamatergic function are early pathophysiological changes associated with Huntington?s disease (HD). The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors. We note that Foxp2 encodes the longest polyglutamine repeat protein in the human reference genome, and we show that it can be sequestered into aggregates with polyglutamine-expanded mutant Huntingtin protein (mHTT). Foxp2 overexpression in HD model mice leads to altered expression of several genes associated with synaptic function, genes which present new targets for normalization of corticostriatal dysfunction in HD. Overall design: 4 mice per group of each: Con+Con, Con+Foxp2, BACHD+Con, BACHD+Foxp2 Foxp2 or Control virus was injected into BACHD and Control mice, mRNA was isolated and sequenced
Control of Huntington's Disease-Associated Phenotypes by the Striatum-Enriched Transcription Factor Foxp2.
Specimen part, Subject
View SamplesWe used Arabidopsis full-genome microarrays to characterize plant transcript accumulations in wild-type plants and pskr1-5 mutants, 3 days after water treatment and inoculation with the biotrophic oomycete downy mildew pathogen, Hyaloperonospora arabidopsidis.
Evolutionarily distant pathogens require the Arabidopsis phytosulfokine signalling pathway to establish disease.
Specimen part
View SamplesA human bone marrow-derived mesenchymal stromal cell (MSCs) and cord blood-derived CD34+ stem cell co-culture system was set up in order to evaluate the proliferative and differentiative effects induced by MSCs on CD34+ stem cells, and the reciprocal influences on gene expression profiles
Mesenchymal stromal cells (MSCs) induce ex vivo proliferation and erythroid commitment of cord blood haematopoietic stem cells (CB-CD34+ cells).
Specimen part
View SamplesStandardization of MSC manufacturing is urgently needed to facilitate comparison of clinical trial results. Here, we compare gene expression of MSC generated by the adaptation of a proprietary method for isolation and cultivation of a specific umbilical cord tissue-derived population of Mesenchymal Stromal Cells (MSCs)
Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data.
No sample metadata fields
View SamplesTranscriptome analysis of hindlimb muscles from dystrophic mice
Comparative transcriptome analysis of muscular dystrophy models Large(myd), Dmd(mdx)/Large(myd) and Dmd(mdx): what makes them different?
Sex, Specimen part
View SamplesHow the various cell-types of the body achieve their specific shapes is fundamentally unknown. Here, we explore this issue by identifying genes involved in the elaboration of the complex, yet conserved, cellular morphology of Müller glial (MG) cells in the retina. Using genomic based strategies in zebrafish, we found more than 40 candidate genes involved in specific aspects of MG morphogenesis. The successive steps of cell morphogenesis correlate with the timing of the expression of cohorts of inter-related genes that have roles in generating the particular anatomical features of these cells, suggesting that a sequence of genetic regulomes govern stepwise cellular morphogenesis in this system. Overall design: 12 samples with three replicates each are provided. GFAP:GFP positive and negative cells were FAC sorted from wild type animals from each developmental stage
Genetic control of cellular morphogenesis in Müller glia.
Specimen part, Subject
View SamplesPolybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in a variety of commercial and household products. They have been detected in the environment and accumulate in mammalian tissues and fluids. PBDE toxicity is thought to be associated with endocrine disruption, developmental neurotoxicity and changes in fetal development. Although humans are exposed to PBDEs, our knowledge of the effects of PBDE metabolites on human cells with respect to health risk is insufficient. Two hydroxylated PBDEs (OH-PBDEs), 2-OH-BDE47 and 2-OH-BDE85, were investigated for their effects on cell viability/proliferation, DNA damage, cell cycle distribution and gene expression profiling in H295R adrenocortical carcinoma cells. We show that the two agents are cytotoxic in a dose-dependent manner only at micromolar concentrations, with 2-OH-BDE85 being more toxic than 2-OH-BDE47. However, no DNA damage was observed for either chemical, suggesting that the biological effects of OH-PBDEs occur primarily via non-genotoxic routes. Furthermore, no evidence of aryl hydrocarbon receptor (AHR)-mediated, dioxin-like toxicity was observed. Instead, we report that a micromolar concentration of OH-PBDEs induces transcriptional changes associated with endoplasmic reticulum stress and the unfolded protein response. We discuss whether OH-PBDE bioaccumulation could result in impairment of the adrenocortical secretory function.
Cytotoxicity and gene expression profiling of two hydroxylated polybrominated diphenyl ethers in human H295R adrenocortical carcinoma cells.
No sample metadata fields
View SamplesAberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer. Overall design: RNA-seq of SETD2 mutant and wild-type ccRCC cell lines.
Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma.
No sample metadata fields
View SamplesDuring S-phase of the cell cycle production of the core histone proteins is precisely balanced with DNA replication. Metazoan mRNAs encoding replication dependent (RD) histones lack polyA tail normally formed by 3' end cleavage and coupled polyadenylation of the pre-mRNA. Instead, they undergoes to endonucleolytic cleavage on the 3' side of an RNA hairpin (stem loop) producing mRNA with a 3´-stem loop (SL), which is exported from the nucleus for use in translation. The same endonuclease that is involved in normal protein-coding pre-mRNA cleavage, i.e. cleavage and poyladenylation specificity factor 73 (CPSF73), is proposed to catalyse RD pre-histone mRNA cleavage. Additional factors specific to RD pre-histone mRNA processing, including stem loop binding protein (SLBP) and the U7 small nuclear ribonucleoprotein (U7snRNP) that binds to a histone downstream element (HDE) are thought to be involved in CPSF73 targeting to RD pre-histone mRNA. We report that a different histone specific endonuclease (HSE), which like CPSF73 is a metallo ß lactamase (MBL) fold protein, is specific for RD pre-histone mRNA cleavage10,11. Crystallographic and biochemical studies reveal HSE has a di-zinc ion containing active site related to that of CPSF73, but which has distinct overall fold. Notably HSE depletion from cells leads to the production of unprocessed RD pre-histone mRNA due to inefficient 3' end processing. The consequent depletion of core histone proteins correlates with a cell cycle defect due to a delay in entering/progressing through S-phase. HSE thus may represent a new type of S-phase specific cancer target. Overall design: Examination of chromatin mRNA profiles in HeLa cells after depletion of HSE or CPSF73 by siRNA treatment.
Biosynthesis of histone messenger RNA employs a specific 3' end endonuclease.
Specimen part, Subject
View SamplesAutophagy generally participates in innate immunity by elimination of intracellular pathogens. However, many of them developed successful strategies to counteract their autolysosomal digestion and lastly to exploit this catabolic cellular process.
Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210.
Specimen part
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