Genome wide mRNA and miRNA profiling was performed in SH-SY5Y cells stably overexpressing wild type or mutant MIR204 or MIR618. Mutants came from a large scale genetic screening of brain expressed miRNA genes in patients with schizophrenia or idiopathic generalized epilepsy and in control individuals. Based on enrichment of the variants with the schizophrenic or epileptic phenotype and based on impact prediction, two variants, one near MIR204 (rs7861254) and one in MIR618 (rs2682818) were selected for functional validation. Genome wide profiling of mRNA (micro-array) and mature miRNAs (small RNA sequencing, submitted to SRA) was performed in the created stable cells to assess the effect of the variants and to investigate the function of these miRNA genes.
Schizophrenia-Associated MIR204 Regulates Noncoding RNAs and Affects Neurotransmitter and Ion Channel Gene Sets.
Cell line
View SamplesTo understand the molecular control of development and regeneration in the mammalian cochlear sensory epithelia, we performed a comparative study of gene expression patterns between postnatal day-3 (P3) and adult stages using a microarrays approach.
Transcriptomic analysis of the developing and adult mouse cochlear sensory epithelia.
Specimen part
View SamplesTo identify cellular and genetic abnormalities involved in interstrand cross link repair-deficient bone marrow failure and its transformation to leukemia, we used an Ercc1 hypomorphic mouse model (Ercc1 -/d).
ICL-induced miR139-3p and miR199a-3p have opposite roles in hematopoietic cell expansion and leukemic transformation.
Age, Specimen part
View SamplesUrocanic acid (UCA) is a major epidermal chromophore that undergoes trans to cis photoisomerisation following exposure to solar ultraviolet radiation (UVR). Although there is considerable evidence that cis-UCA suppresses cell-mediated immune response in mouse skin, the molecular events are not fully understood. In this study, we examined involvement of gene transcription in the immunomodulatory effects of cis-UCA on primary human keratinocytes.
cis-Urocanic acid initiates gene transcription in primary human keratinocytes.
Sex
View SamplesBackground: Transcription control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study, we combined RNA sequencing of human complex I-deficient patient cells across 32 conditions of perturbed mitochondrial metabolism, with a comprehensive analysis of gene expression patterns, co-expression calculations and transcription factor binding sites. Results: Our analysis shows that OXPHOS genes have a significantly higher co-expression with each other than with other genes, including mitochondrial genes. We found no evidence for complex-specific mRNA expression regulation in the tested cell types and conditions: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of OXPHOS complex subunits compared to assembly factors, suggesting divergent transcription programs. Furthermore, complex I co-expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of six yet uncharacterized candidate transcription factors (ELK1, KLF7, SP4, EHF, ZNF143, and EL2). Conclusions: OXPHOS genes share an expression program distinct from other mitochondrial genes, indicative of targeted regulation of this mitochondrial sub-process. Within the subset of OXPHOS genes we established a difference in expression between subunits and assembly factors. Most transcription regulators of genes that co-express with complex I are well-established factors for OXPHOS biogenesis. For the remaining six factors we here suggest for the first time a link with transcription regulation in OXPHOS deficiency. Overall design: RNA-SEQ of whole cell RNA in 2 control and 2 complex I deficient patient fibroblast cell lines treated with 4 compounds in duplicate, resulting in a total of 2x2x4x2=32 samples
Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system.
No sample metadata fields
View SamplesAnalysis of H292 cells infected with Mycoplasma hyorhinis. Mycoplasma infection reduces the cytotoxic effect of Nutlin3 on H292 cells. The results provide insight into molecular mechanisms underlying the response of H292 cells to Nutlin3.
Mycoplasma hyorhinis reduces sensitivity of human lung carcinoma cells to Nutlin-3 and promotes their malignant phenotype.
Specimen part, Cell line
View SamplesDefective complex I (CI) is the most common type of oxidative phosphorylation (OXPHOS) disease in patients, with an incidence of 1 in 5,000 live births. Complex I deficiency can present in infancy or early adulthood and shows a wide variety of clinical manifestations, including Leigh syndrome, (cardio)myopathy, hypotonia, stroke, ataxia and lactic acidosis. A number of critical processes and factors, like superoxide production, calcium homeostasis, mitochondrial membrane potential and mitochondrial morphology, are known to be involved in clinical CI deficiency, but not all factors are yet known and a complete picture is lacking.
Transcriptional changes in OXPHOS complex I deficiency are related to anti-oxidant pathways and could explain the disturbed calcium homeostasis.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesE14 TG2a cells grown with LIF were disaggregated and FACS sorted for cell surface 5T4 negativity versus E14 TG2a cells grown without LIF for 3 days and sorted for 5T4 positivity.
CXCR4 mediated chemotaxis is regulated by 5T4 oncofetal glycoprotein in mouse embryonic cells.
Specimen part
View SamplesThe aim of this work was to identify functional features that are specific of human Treg cells, through the identification of genes that are differentially expressed: 1/ in activated Treg clones versus activated Thelper clones; 2/ in Th clones activated in the presence versus the absence of TGFb; 3/ in suppressed Th clones, i.e. Th clones activated in the presence of Treg clones, versus controls.
Comparison of stable human Treg and Th clones by transcriptional profiling.
No sample metadata fields
View SamplesAfter zygote division, the resulting daughter cells progressively give rise to two very different tissue types. With the use of microarrays, global nuclear expression profiles were generated.
Cell type-specific transcriptome analysis in the early Arabidopsis thaliana embryo.
Specimen part
View Samples