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Regeneration competence accompanies increased expression of arginine methyltransferase PRMT8 in human adult fibroblasts

Identification of therapeutically relevant molecules is necessary for the advancement of non-viral reprogramming of human cells for regenerative medicine. We have developed a novel non-viral model system that transforms primary human dermal fibroblasts into cells with induced regeneration competence (iRC). Low oxygen-mediated effects of fibroblast growth factor FGF2 lead to an increased cellular lifespan with a two fold increase in population doublings before senescence, remaining non-tumorigenic when injected into SCID mice while maintaining regeneration competence [1, 2]. This system allows us to study molecules that participate in increased cellular lifespan in a non-tumorigenic system. This project aims identify unique molecules that contribute to the iRC phenotype with the goal to design therapeutics that target diseases associated with aging, wound healing, and tumor formation. Analysis of 84 chromatin modification enzymes by qRT-PCR revealed 13-fold upregulation of the arginine methyltransferase PRMT8 in iRC cells. Increased protein expression was confirmed in both iRC and human embryonic stem cells - the first demonstration of endogenous human PRMT8 expression. These results may ultimately lead to novel findings regarding regulation of arginine methyltransferases and define functions of endogenous PRMT8 in human cells.