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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 performed RNAseq analysis of human embryonic stem (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 derived from long non-coding RNAs (lncRNAs) were found to account for a significantly larger proportion of transcripts from their loci of origin than circRNAs from coding genes. The most abundant, circ RMST :E12-E6, showed a > 100X increase during differentiation accompanied by an isoform switch, and accounts for > 99% of  RMST  transcripts in many adult tissues. The second most abundant, circ FIRRE :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 , genes with established roles in neurogenesis and topological organisation of chromosomal domains respectively, are processed as circular lncRNAs with only minor linear species.    Electronic supplementary material  The online version of this article (10.1186/s12864-018-4660-7) contains supplementary material, which is available to authorized users.

Analysis of human ES cell differentiation establishes that the dominant isoforms of the lncRNAs RMST and FIRRE are circular