Prion protein in ESC regulation.

A large number of studies have analysed the putative functions of the prion protein (PrP(C)) in mammals. Although its sequence conservation over a wide range of different animals may indicate that this protein could have a key role in prion diseases, an absolutely accepted involvement has not been found so far. We have recently reported that PrP(C) regulates Nanog mRNA expression, the first non-redundant function of PrP(C) in embryonic stem cells (ESC), which translates into control of pluripotency and early differentiation. Contrary to what it is believed, the other two members of the prion protein family, Doppel and Shadoo, cannot replace the absence of PrP(C), causing the appearance of a new embryoid body (EB) population in our in vitro culture. The similarities between EB and an early post-implantation embryo suggest that this might also occur in vivo, enhancing the importance of this finding. On the other hand, our data may support the hypothesis of a relationship between the loss of PrP(C) function and neuronal degeneration in prion diseases. A reduction in brain stem cells pluripotency after PrP(C) is misfolded into the pathological conformation (PrP(Sc)) could lead to a delay or a disappearance of the normal brain damage recovery.