A map of human circular RNAs in clinically-relevant tissues

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. To explore circRNA expression patterns in human tissues, we performed rRNA-depleted RNA sequencing and circRNA detection in twenty clinically relevant samples.