Common MicroRNA-mRNA Interactions Exist Among Distinct Porcine IPSC Lines Independent of Their Metastable Pluripotent States

Previous evidences have proved that porcine-induced pluripotent stem cells (piPSCs) could be induced to distinctive metastable pluripotent states. This raises the issue of whether there is a common transcriptomic profile existing among the piPSC lines at distinctive state. In this study, we performed conjoint analysis of small RNA-seq and mRNA-seq for three piPSC lines which represent LIF dependence, FGF2 dependence and LFB2i dependence, respectively. Interestingly, we found there are 16 common microRNAs which potentially target 13 common mRNAs among the three piPSC lines. Dual-luciferase reporter assay validated that miR-370, one of the 16 common microRNAs, could directly target the 3'UTR of LIN28A. When the differentiation occurred, miR-370 could be activated in piPSCs and switched off the expression of LIN28A. Ectopic expression of miR-370 in piPSCs could reduce LIN28A expression, decrease the alkaline phosphatase activity, slow down the proliferation, and further cause the downregulation of downstream pluripotent genes (OCT4, SOX2, NANOG, SALL4 and ESRRB) and upregulation of differentiation relevant genes (SOX9, JARID2 and JMJD4). Moreover, these phenotypes caused by miR-370 could be rescued by overexpressing LIN28A. Collectively, our findings suggest that a set of common miRNA-mRNA interactions exist among the distinct piPSC lines, which orchestrate the self-renewal and differentiation of piPSCs independent of their metastable pluripotent states.