Variability of miRNA expression during the differentiation of human embryonic stem cells into retinal pigment epithelial cells

•Dominant isomiRs are not always the canonical miRNAs during the course of hESC differentiation into RPE cells.•27 statistically significant miRNA editing sites were identified in 24 different miRNAs.•Marked major-to-minor arm-switching events existed in 14 pre-miRNAs during the hESC to RPE cell differentiation phases.

Embryonic stem cells (ESCs) and induced pluripotent stem cells can be induced to differentiate into retinal pigment epithelium (RPE). MiRNAs have been characterized and found playing important roles in the differentiation process of ESCs, but their length and sequence heterogeneity (isomiRs), and their non-canonical forms of miRNAs are underestimated or ignored. In this report, we found some non-canonical miRNAs (dominant isomiRs) in all differentiation stages, and 27 statistically significant editing sites were identified in 24 different miRNAs. Moreover, we found marked major-to-minor arm-switching events in 14 pre-miRNAs during the hESC to RPE cell differentiation phases. Our study for the first time reports exploring the variability of miRNA expression during the differentiation of hESCs into RPE cells and the results show that miRNA variability is a ubiquitous phenomenon in the ESC differentiation.