Differentiation, stem cells and prions - CNRS FRE2937  

  HEADProf. KELLERMANN Odile / okellerm@vjf.cnrs.fr
PRADINES Elodie / Dr SCHNEIDER Benoît / Dr VIDAL Catherine

  Annual Report

The central topic of our research deals with the mechanisms that control stem cell differentiation. We exploit the properties of a neuroectodermal (1C11) and a mesenchymal (C1) progenitor that we isolated from multipotent embryonal carcinoma cells. Both clones display the properties of stem cells, and may engage upon appropriate induction into differentiation programs up to the acquisition of specialized functions. Their alternative fates are mutually-exclusive and recruit nearly 100% cells.

The 1C11 cell line to study neuronal homeostasis and prion physiopathology:

1C11 cells can convert into fully-functional serotoninergic (1C115-HT) or noradrenergic (1C11NE) neuronal cells. The implementation of neuronal functions is regulated by external serotonin (5-HT) or noradrenaline (NE) through autoreceptors selectively induced along either pathway. Our aim is to characterize the signaling pathways, the targets and the cross talks associated with the receptors to unravel how these autoreceptors contribute to the homeostasis of 5-HT or NE functions. Indeed, we have shown that the 5-HT2B receptor controls the onset and functionality of the 5-HT transporter. In addition, we have established a functional link between the bioaminergic 5-HT2B and α1D receptors and the production of reactive oxygen species, the shedding of TNFα, and the metabolism of 5-HT or NE in 1C115-HT and 1C11NE neuronal cells.

The 1C11 cell line has been instrumental in assigning a signaling function to the cellular prion protein PrPC. Using the prion neurotoxic peptide PrP106-126 to mimic prion infection, we have established that PrP106-126 exerts a toxic action that is restricted to neuronal cells. By binding to normal PrPC, PrP106-126 corrupts the normal signaling pathway coupled with PrPC and recruits apoptotic cascasdes.

Finally, 1C11 cells support the replication of various prion strains. The impact of prion infection on the implementation of 5-HT and NE-associated functions is currently being investigated.

C1 cells and bone mineralization:

The C1 clone is a tripotential mesoblastic progenitor with osteogenic, chondrogenic or adipogenic potencies. We recently identified the 5-HT2B serotoninergic receptor as an essential player during the kinetics of osteogenic differentiation, whose intrinsic and agonist-dependent activity contributes to optimal mineralization through TNAP activation. We are currently developing a 3D scanner imaging project to characterize mineralizing defects in 5-HT2B knock-out mice.



Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
If you have problems with this Web page, please write to rescom@pasteur.fr