|Differentiation, stem cells and prions - CNRS FRE2937|
|HEAD||KELLERMANN Odile / firstname.lastname@example.org|
|MEMBERS||Dr BAUDRY Anne / DIMITROVA Sasha / Dr ERMONVAL Myriam / HARICHANE Yassine / LOUBET Damien / MONIER Marie Noël
Dr MOUILLET-RICHARD Sophie / Dr POLIARD Anne / PRADINES Elodie / Dr SCHNEIDER Benoît / Dr VIDAL Catherine
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 isolated from multipotent embryonal 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 serotonergic (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 crosstalks 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. This year, we have demonstrated that pathogenic prions alter monoamiinergic functions and trigger the production of oxidized derivatives of serotonin or catecholamines.
C1 cells and bone mineralization:
The C1 clone is a tripotential mesoblastic progenitor with osteogenic, chondrogenic or adipogenic potencies. We recently identified a critical role of the 5-HT2B serotonergic receptor in mineralization through full control of tissue-non specific alkaline phosphatase activity (TNAP). In patients suffering from ectopic vascular mineralization, the degree of calcification correlates with the level of 5-HT2BR expression. We are developping a 3D scanner imaging project to characterize mineralizing defects in 5-HT2B knock-out mice. We are also setting up protocols for dental repair.
Launay J.M., Schneider B, Loric S., Patruandjekul J., Da Prada M. & Kellermann O. 2006 Control by 5-HT2B receptor of 5-HT transport and antidepressant recognition during serotonergic differentiation. FASEB J, 20(11):1843-54.
Locker M, Bitard J, Collet C, Poliard A, Mutel V, Launay J.M and Kellermann O. 2006. Stepwise control of osteogenic differentiation by 5-HT2B receptor signalling: Nitric oxyde production and phospholipase A2 activation.. Cell Signal. May;18(5):628-39.
Mouillet-Richard S., Pietri M., Schneider B., Vidal C., Mutel V., Launay J-M. & Kellermann O.. 2005 Modulation of serotonergic receptor signaling and crosstalk by prion protein. J. Biol Chem, 280,4592-4601.
Pietri M., Schneider B, Mouillet-Richard S, Ermonval M, Mutel V, Launay J.M and Kellermann O. 2005 Reactive oxygen species- dependent TNF-α converting enzyme activation through stimulation of 5-HT2B a nd αD autoreceptors in neuronal cells. FASEB J, 19,1078-1087.
Pietri M., Caprini A,, Mouillet-Richard S, Pradines E, Ermonval M ., O Kellermann and B Schneider. 2006 Overstimulation of PrPC signaling pathways by prion peptide 106-126 causes oxydative injury of 1C11 bioaminergic neuronal cells. J. Biol Chem, 281(38):28470-9.
Activity Reports 2007 - Institut Pasteur
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