Dynamic regulation of small RNAome during the early stage of cardiac differentiation from pluripotent embryonic stem cells

Abstract Embryonic stem cells (mESCs), having potential to differentiate into three germ-layer cells including cardiomyocytes, shall be a perfect model to help understanding heart development. Here, using small RNA deep sequencing, we studied the small RNAome in the early stage of mouse cardiac differentiation. We found that the expression pattern of most microRNA (miRNA) were highly enriched at the beginning and declined thereafter, some were still insufficiently expressed on day 6, and most miRNAs recovered in the following days. When pluripotent embryonic stem cells are differentiating to cardiomyocytes, targeted genes are concentrated on TGF, WNT and cytoskeletal remodeling pathway. The pathway and network of dynamically changed target genes of the miRNAs at different time points were also investigated. Furthermore, we demonstrated that small rDNA-derived RNAs (srRNAs) were significantly up-regulated during differentiation, especially in stem cells. The pathways of srRNAs targeted genes were also presented. We described the existence and the differential expression of transfer RNA (tRNA), Piwi-interacting RNA (piRNA) and Endogenous siRNAs ( endo -siRNAs) in this process. This study reports the genome-wide small RNAome profile, and provides a uniquely comprehensive view of the small RNA regulatory network that governs embryonic stem cell differentiation and cardiac development.