Treatment with normal prion protein delays differentiation and helps to maintain high proliferation activity in human embryonic stem cells.

The normal cellular form of prion protein (PrP(C)) has been shown to exhibit a diverse range of biological activities. Several recent studies highlighted potential involvement of PrP(C) in embryogenesis or in regulating stem cell self-renewal and proliferation. In the current study, we employed human embryonic stem cells (hESCs) for assessing the potential role of prion protein in early human development. Here, we showed that treatment of hESCs with full-length recombinant PrP folded into an alpha-helical conformation similar to that of PrP(C) delayed the spontaneous differentiation of hESCs and helped to maintain their high proliferation activity during spontaneous differentiation. Considering that administration of alpha-rPrP was also found to down-regulate the expression of endogenous PrP(C), the effects of alpha-rPrP were likely to be indirect, i.e. executed by endogenous PrP(C). Together with previous observations, these work support the hypothesis that PrP(C) is involved in regulating self-renewal/differentiation status of stem cells including hESCs.