NG2 and Olig2 expression provides evidence for phenotypic deregulation of cultured central nervous system and peripheral nervous system neural precursor cells.
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-alpha). 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.
Dromard
Cecile
C
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.
Bartolami
Sylvain
S
Deleyrolle
Loïc
L
Takebayashi
Hirohide
H
Ripoll
Chantal
C
Simonneau
Lionel
L
Prome
Sylvie
S
Puech
Sylvie
S
Tran
Van Ba Christophe
VB
Duperray
Christophe
C
Valmier
Jean
J
Privat
Alain
A
Hugnot
Jean-Philippe
JP
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology*; D004622:Embryo, Mammalian / Q000166:cytology; D005732:Gangliosides / Q000378:metabolism; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000378:metabolism; D000090322:Homeobox Protein Nkx-2.2; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D017933:Peripheral Nervous System / Q000166:cytology*; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D005732:Gangliosides; D006609:High Mobility Group Proteins; D000090322:Homeobox Protein Nkx-2.2; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4; C499317:Ascl1 protein, mouse; C000715627:Nkx2-2 protein, mouse; C512773:Olig2 protein, mouse; C527933:Sox9 protein, mouse; C062875:ganglioside A2B5