MicroRNAs Contribute to iPSC-Somatic Donor Memory [Developmental Biology]

December 5th, 2013 by Vitaloni, M., Pulecio, J., Bilic, J., Kuebler, B., Laricchia-Robbio, L., Izpisua Belmonte, J. C.

Induced pluripotent stem cells (iPSCs) maintain during the first few culture passages a set of epigenetic marks and metabolites characteristic of their somatic cell of origin, a concept defined as epigenetic donor memory. These residual somatic features are lost over time after extensive culture passaging. Therefore, epigenetic donor memory may be responsible for the higher differentiation efficiency towards the tissue of origin observed in low-passage (LP)-iPSCs vs. high-passage (HP)-iPSC) or iPSCs derived from a different tissue source. Remarkably, there are no studies on the relevance of miRNA memory following reprogramming, despite the established role of these molecules in the context of pluripotency and differentiation. Using hematopoietic progenitors cells (HPC) as a model, we demonstrated that miRNAs play a central role in somatic memory retention in iPSCs. Moreover, the comparison of the miRNA expression profiles among iPSCs from different sources allowed for the detection of a set of candidate miRNAs responsible for the higher differentiation efficiency rates towards blood progenitors observed in LP-iPSCs. Combining bioinformatic predictive algorithms with biological target validation, we identified miR-155 as a key player for the in vitro differentiation of iPSC towards hematopoietic progenitors. In summary, this study reveals that during the initial passages following reprogramming iPSCs maintained the expression of a miRNA set exclusive to the original somatic population. Hence the use of these miRNAs might hold a direct application towards our understanding of the differentiation process of iPSCs towards HPCs.