TY - JOUR AU - Jackson, Michael AB - Background: Circular RNAs (circRNAs) are predominantly derived from protein coding genes, and some can act as microRNA sponges or transcriptional regulators. Changes in circRNA levels have been identified during human development which may be functionally important, but lineage-specific analyses are currently lacking. To address this, we performedRNAseqanalysisofhuman embryonicstem(ES)cells differentiated for 90 days towards 3D laminated retina. Results: A transcriptome-wide increase in circRNA expression, size, and exon count was observed, with circRNA levels reaching a plateau by day 45. Parallel statistical analyses, controlling for sample and locus specific effects, identified 239 circRNAs with expression changes distinct from the transcriptome-wide pattern, but these all also increased in abundance over time. Surprisingly, circRNAs derivedfromlongnon-codingRNAs(lncRNAs) werefoundtoaccountfor asignificantly larger proportion of transcripts from their loci of origin than circRNAs from coding genes. The most abundant, circRMST: E12-E6,showeda >100Xincreaseduringdifferentiation accompaniedbyanisoform switch,and accounts for>99%of RMST transcripts in many adult tissues. The second most abundant, circFIRRE:E10-E5, accounts for > 98% of FIRRE transcripts in differentiating human ES cells, and is one of 39 FIRRE circRNAs, many of which include multiple unannotated exons. Conclusions: Our results suggest that during human ES cell differentiation, changes in circRNA levels are primarily globally controlled. They also suggest that RMST and FIRRE, TI - Analysis of human ES cell differentiation establishes that the dominant isoforms of the lncRNAs RMST and FIRRE are circular JF - BMC Genomics DO - 10.1186/s12864-018-4660-7 DA - 2018-04-20 UR - https://www.deepdyve.com/lp/springer-journals/analysis-of-human-es-cell-differentiation-establishes-that-the-SR3EPuymxN SP - 1 EP - 18 VL - 19 IS - 1 DP - DeepDyve ER -