Cellular prion protein (PrP^C) is expressed in a wide variety of stem cells in which regulates their self-renewal as well as differentiation potential. In this study we investigated the presence of PrP^C in human dental pulp-derived stem cells (hDPSCs) and its role in neuronal differentiation process. We show that hDPSCs expresses early PrP^C at low concentration and its expression increases after two weeks of treatment with EGF/bFGF. Then, we analyzed the association of PrP^C with gangliosides and EGF receptor (EGF-R) during neuronal differentiation process. PrP^C associates constitutively with GM2 in control hDPSCs and with GD3 only after neuronal differentiation. Otherwise, EGF-R associates weakly in control hDPSCs and more markedly after neuronal differentiation.

To analyze the functional role of PrP^C in the signal pathway mediated by EGF/EGF-R, a siRNA PrP was applied to ablate PrP^C and its function. The treatment with siRNA PrP significantly prevented Akt and ERK1/2 phosphorylation induced by EGF.

Moreover, siRNA PrP treatment significantly prevented neuronal-specific antigens expression induced by EGF/bFGF, indicating that cellular prion protein is essential for EGF/bFGF-induced hDPSCs differentiation.

These results suggest that PrP^C interact with EGF-R within lipid rafts, playing a role in the multimolecular signaling complexes involved in hDPSCs neuronal differentiation.

细胞病毒蛋白（PrP ^C）在多种干细胞中表达，这些干细胞调节其自我更新和分化潜能。在这项研究中，我们调查了人类牙髓衍生干细胞（hDPSCs）中PrP ^C的存在及其在神经元分化过程中的作用。我们显示hDPSCs以低浓度表达早期的PrP ^C，用EGF / bFGF治疗两周后其表达增加。然后，我们分析了神经元分化过程中PrP ^C与神经节苷脂和EGF受体（EGF-R）的关联。朊蛋白^ç仅在神经元分化后，与控制hDPSCs中的GM2和GD3组成性结合。否则，EGF-R在控制hDPSC中的结合较弱，在神经元分化后的结合更明显。

为了分析PrP ^C在EGF / EGF-R介导的信号通路中的功能作用，将siRNA PrP应用于消融PrP ^C及其功能。siRNA PrP处理可显着阻止EGF诱导的Akt和ERK1 / 2磷酸化。

此外，siRNA PrP处理显着阻止了EGF / bFGF诱导的神经元特异性抗原表达，表明细胞病毒蛋白对于EGF / bFGF诱导的hDPSCs分化至关重要。

这些结果表明，PrP ^C与脂质筏中的EGF-R相互作用，在涉及hDPSCs神经元分化的多分子信号复合物中发挥作用。