This SuperSeries is composed of the SubSeries listed below.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part, Cell line, Treatment
View SamplesThe deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces ER stress response as major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part
View SamplesThe deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high-density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces the ER stress response as a major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part, Cell line, Treatment
View SamplesThe deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high-density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces the ER stress response as a major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part, Cell line, Treatment
View SamplesWe identified DNAPK as one of the major proteins that physically interact with Autoimmune regulator (Aire). To establish physiological significance of DNAPK in Aire-driven expression of PTA genes in MECs, we utilized BM-reconstituted SCID mice (which express non functional DNAPK in their MECs) and RAG1 null mouse as a control.
Aire's partners in the molecular control of immunological tolerance.
Specimen part
View SamplesTo analyze the impact of Aire on gene expression profile in a model cell line, we used 293T cells and transfected them either with an Aire expression plasmid pCMV-Aire (where mAire is driven by CMV promoter) or with a control plasmid pCMV2B.
Aire's partners in the molecular control of immunological tolerance.
Specimen part
View SamplesBackground: In order to become functionally competent but harmless mediators of the immune system, T cells undergo a strict educational program in the thymus, where they learn to discriminate between self and non-self. This educational program is, to a large extent, mediated by medullary thymic epithelial cells (mTECs) that have a unique capacity to express, and subsequently present a large fraction of body antigens. While the scope of promiscuously expressed genes by mTECs is well established, relatively little is known about the expression of variants that are generated by co- and post-transcriptional processes. Results: Our study reveals that in comparison to other cell types, mTECs display significantly higher levels of alternative splicing, as well as A-to-I and C-to-U RNA editing, which thereby further expand the diversity of their self-antigen repertoire. Interestingly, Aire, the key mediator of mTECs promiscuous gene expression, plays a limited role in the regulation of these transcriptional processes. Conclusions: Our results highlight RNA processing as another layer by which the immune system assures a comprehensive self-representation in the thymus which is required for the establishment of self-tolerance and prevention of autoimmunity. Identification of the number of genes expressed in Aire-KO MEChi Overall design: ~100ng of total RNA was isolated by Trizol extraction from MHC-II high mTECs from a pool of 3 Aire-KO mice. Poly-A-selected transcriptome libraries were generated using the non-directionnal TruSeq V3 RNA Sample Prep Kit (without additional pre-amplification) following the manufacturer''s protocols. Enrichment of DNA fragment with adapter molecules on both ends was done using 15 cycles of PCR amplification using the Illumina PCR mix and primer cocktail. Paired-end (2 × 100 bp) sequencing was performed using the Illumina HiSeq2000 machine.
Extensive RNA editing and splicing increase immune self-representation diversity in medullary thymic epithelial cells.
Specimen part, Subject
View SamplesAnalysis of genes that were differentially expressed in MSC-derived hES cells (VUB01 and SA01) as compared to VUB01 and SA01 undifferentiated hES cells
Combined mRNA and microRNA profiling reveals that miR-148a and miR-20b control human mesenchymal stem cell phenotype via EPAS1.
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View SamplesTo determine the modulation of gene expression of C57BL/6 and DBA/2 BMDLs in the presence of living intracellular Leishmania amazonensis amastigotes
Distinct transcriptional signatures of bone marrow-derived C57BL/6 and DBA/2 dendritic leucocytes hosting live Leishmania amazonensis amastigotes.
Specimen part
View SamplesThe aim of this study is to analyze the transcriptional effects of Aire deficiency in the thymus, using the Affymetrix MoGene platform to analyze variation in exon usage
Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells.
Specimen part
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