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SRP109805
Homo sapiens
24 Downloadable Samples
Illumina HiSeq 2000
Description
Cellular circular RNAs (circRNAs) are generated by head-to-tail splicing and are present in all multicellular organisms studied so far. Recently, circRNAs have emerged as large class of RNA which can function as post-transcriptional regulators. It has also been shown that many circRNAs are tissue- and stage specifically expressed. Moreover, the unusual stability and expression specificity make circRNAs important candidates for clinical biomarker research. Here, we present a circRNA expression resource of twenty human tissues highly relevant to disease-related research: vascular smooth muscle cells (VSMCs), human umbilical vein (HUVECs), artery endothelial cells (HUAECs), atrium, vena cava, neutrophils, platelets, cerebral cortex, placenta, and samples from mesenchymal stem cell differentiation. In eight different samples from a single donor, we found highly tissue-specific circRNA expression. Circular-to-linear RNA ratios revealed that many circRNAs were higher expressed than their linear host transcripts. Among the 65 validated circRNAs, we noticed potential biomarkers. In adenosine deaminase-deficient, severe combined immunodeficiency (ADA-SCID) patients and in Wiskott-Aldrich-Syndrome (WAS) patients' samples, we found evidence for differential circRNA expression of genes that are involved in the molecular pathogenesis of both phenotypes. Our findings underscore the need to assess circRNAs in mechanisms of human disease. Overall design: To explore circRNA expression patterns in human tissues, we performed rRNA-depleted RNA sequencing and circRNA detection in twenty clinically relevant samples.
Publication Title
A map of human circular RNAs in clinically relevant tissues.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene transfer into HSCs by gammaretroviral vectors (RV) is an effective treatment for inherited blood disorders, although potentially limited by the risk of insertional mutagenesis. We evaluated the genomic impact of RV integration in T-lymphocytes from adenosine deaminase (ADA)-Severe combined immunodeficiency (SCID) patients 10 to 30 months after infusion of autologous, genetically-corrected CD34+ cells. Expression profiling on ex vivo T-cell bulk population revealed no difference with respect to healthy controls. To assess the effect of vector integration on gene expression at the single cell level, primary T-cell clones were isolated from two patients. T-cell clones harboured either one or two vector copies per cell and displayed partial to full correction of ADA expression, purine metabolism and TCR-driven functions. Analysis of retroviral integration sites (RIS) indicated a high diversity in T-cell origin, consistent with the polyclonal TCR-Vbeta repertoire. Quantitative transcript analysis of 120 genes within a 200kb-window around RIS showed modest (2.8- to 5.2-fold) disregulation of 5.8% genes in 18.6% of the T-cell clones compared to controls. Nonetheless, affected clones maintained a stable phenotype and normal functions in vitro. These results confirm that RV-mediated gene transfer for ADA-SCID is safe, and provide crucial information for the development of future gene therapy protocols.
Publication Title
Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy.
Sample Metadata Fields
Specimen part
View Samples