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TISSUE-SPECIFIC STEM CELLS

NG2 and Olig2 Expression Provides Evidence for Phenotypic Deregulation of Cultured Central Nervous System and Peripheral Nervous System Neural Precursor Cells

^aINSERM U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St ELOI, Montpellier Cedex 05, France;
^bDivision of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan;
^cService Regional INSERM de cytométrie en flux, Montpellier Cedex 05, France

Key Words. Neural stem cells • Oligodendrocytes • NG2 • Proteoglycan • Peripheral nervous system • Neurospheres • Cytometry Plasticity

Correspondence: Jean-Philippe Hugnot, M.D., Ph.D., INSERM U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs Institut des Neurosciences de Montpellier, Hôpital St ELOI, BP 74103 80, avenue Augustin Fliche 34091 Montpellier Cedex 05, France. Telephone: 33 4.99.63.60.08 Fax: 33 4.99.63.60.20 e-mail: hugnot{at}univ-montp2.fr

Received November 10, 2005; accepted for publication October 10, 2006.
First published online in STEM CELLS EXPRESS   October 19, 2006.



Neural stem cells cultured with fibroblast growth factor 2 (FGF2)/epidermal growth factor (EGF) generate clonal expansions called neurospheres (NS), which are widely used for therapy in animal models. However, their cellular composition is still poorly defined. Here, we report that NS derived from several embryonic and adult central nervous system (CNS) regions are composed mainly of remarkable cells coexpressing radial glia markers (BLBP, RC2, GLAST), oligodendrogenic/neurogenic factors (Mash1, Olig2, Nkx2.2), and markers that in vivo are typical of the oligodendrocyte lineage (NG2, A2B5, PDGFR-). On NS differentiation, the latter remain mostly expressed in neurons, together with Olig2 and Mash1. Using cytometry, we show that in growing NS the small population of multipotential self-renewing NS-forming cells are A2B5⁺ and NG2⁺. Additionally, we demonstrate that these NS-forming cells in the embryonic spinal cord were initially NG2^– and rapidly acquired NG2 in vitro. NG2 and Olig2 were found to be rapidly induced by cell culture conditions in spinal cord neural precursor cells. Olig2 expression was also induced in astrocytes and embryonic peripheral nervous system (PNS) cells in culture after EGF/FGF treatment. These data provide new evidence for profound phenotypic modifications in CNS and PNS neural precursor cells induced by culture conditions.

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