microRNA and mRNA interactions in induced pluripotent stem cell reprogramming of lymphoblastoid cell lines

摘要

A large number of Epstein Barr virus (EBV) immortalized lymphoblastoid cell lines (LCLs) have been generated and maintained in genetic/epidemiological studies as a perpetual source of DNA and as a surrogate in vitro cell model. Recent successes in reprograming LCLs into induced pluripotent stem cells (iPSCs) has paved the way to generate more relevant in vitro disease models using this existing bioresource. However, the latent EBV infection in the LCLs make them a unique cell type by altering expression of many cellular genes and miRNAs. These EBV induced changes in the LCL miRNome and transcriptome are reversed upon reprogramming into iPSCs, which allows a unique opportunity to better understand the miRNA and mRNA interactions that are EBV induced in LCLs and the changes that takes place during iPSC reprogramming. To identify the potential miRNA-mRNA interactions and better understand their role in regulating the cellular transitions in LCLs and their reprogrammed iPSCs, we performed a parallel genome-wide miRNA and mRNA expression analysis in six LCLs and their reprogrammed iPSCs. A total of 85 miRNAs and 5,228 mRNAs were significantly differentially expressed (DE). The target prediction of the DE miRNAs using TargetScan-Human, TarBase and miRecords databases identified 1,842 mRNA targets that were DE between LCLs and their reprogrammed iPSCs. The functional annotation, upstream regulator and gene expression analysis of the predicted DE mRNA targets suggest the role of DE miRNAs in regulating EBV induced changes in LCLs and self-renewal, pluripotency and differentiation in iPSCs.