Oligodendrogenesis of adult neural progenitors: differential effects of ciliary neurotrophic factor and mesenchymal stem cell derived factors.
The oligodendrogenic program of progenitor cells in the adult CNS follows a sequential process of progenitor proliferation, fate choice, determination, differentiation, maturation and survival. Previously, we described a soluble activity derived from mesenchymal stem cells that induces oligodendrogenesis in adult neural progenitor cells. Here, we hypothesized that ciliary neurotrophic factor might be a candidate for this activity, since (i) it is expressed by mesenchymal stem cells and (ii) it can promote oligodendrogenesis during development. Along the course of the study, we found differential effects by ciliary neurotrophic factor and by the mesenchymal stem cells-derived activity on neural progenitors. While the mesenchymal stem cells-derived activity induced oligodendrogenesis at the expense of astrogenesis and promoted oligodendroglial differentiation/maturation, the effect of ciliary neurotrophic factor was restricted to the latter one. This was reflected at the levels of the cell fate determinants Olig1, Olig2, Id2, and the oligodendroglia-maturation transcription factor GTX/Nkx6.2. Finally, experiments using blocking antibodies excluded ciliary neurotrophic factor to be the mesenchymal stem cell-derived oligodendroglial activity. In summary, this work provides evidence for differential effects of ciliary neurotrophic factor and mesenchymal stem cells-derived activity on oligodendrogenesis of adult neural progenitor cells.
Rivera
Francisco J
FJ
Department of Neurology, University of Regensburg, Regensburg, Germany.
Kandasamy
Mahesh
M
Couillard-Despres
Sebastien
S
Caioni
Massimiliano
M
Sanchez
Rosario
R
Huber
Christophe
C
Weidner
Norbert
N
Bogdahn
Ulrich
U
Aigner
Ludwig
L
D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology; D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D017077:Culture Media, Conditioned; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D015151:Immunoblotting; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020934:Ciliary Neurotrophic Factor; D017077:Culture Media, Conditioned