NG2 and Olig2 expression provides evidence for phenotypic deregulation of cultured central nervous system and peripheral nervous system neural precursor cells

Cecile Dromard; Sylvain Bartolami; Loïc Deleyrolle; Hirohide Takebayashi; Chantal Ripoll; Lionel Simonneau; Sylvie Prome; Sylvie Puech; Van Ba Christophe Tran; Christophe Duperray; Jean Valmier; Alain Privat; Jean-Philippe Hugnot

doi:10.1634/stemcells.2005-0556

NG2 and Olig2 expression provides evidence for phenotypic deregulation of cultured central nervous system and peripheral nervous system neural precursor cells

Stem Cells. 2007 Feb;25(2):340-53. doi: 10.1634/stemcells.2005-0556. Epub 2006 Oct 19.

Authors

Cecile Dromard¹, Sylvain Bartolami, Loïc Deleyrolle, Hirohide Takebayashi, Chantal Ripoll, Lionel Simonneau, Sylvie Prome, Sylvie Puech, Van Ba Christophe Tran, Christophe Duperray, Jean Valmier, Alain Privat, Jean-Philippe Hugnot

Affiliation

¹ 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.

PMID: 17053213
DOI: 10.1634/stemcells.2005-0556

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens / metabolism*
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Cell Differentiation
Cells, Cultured
Central Nervous System / cytology*
Embryo, Mammalian / cytology
Gangliosides / metabolism
Gene Expression Regulation
High Mobility Group Proteins / metabolism
Homeobox Protein Nkx-2.2
Mice
Models, Biological
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neuroglia / cytology
Neuroglia / metabolism
Neurons / cytology*
Neurons / metabolism
Oligodendrocyte Transcription Factor 2
Peripheral Nervous System / cytology*
Phenotype*
Proteoglycans / metabolism*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptor, Platelet-Derived Growth Factor alpha / genetics
Receptor, Platelet-Derived Growth Factor alpha / metabolism
SOX9 Transcription Factor
Spinal Cord / cytology
Spinal Cord / embryology
Stem Cells / cytology*
Stem Cells / metabolism
Transcription Factors / metabolism

Substances

Antigens
Ascl1 protein, mouse
Basic Helix-Loop-Helix Transcription Factors
Gangliosides
High Mobility Group Proteins
Homeobox Protein Nkx-2.2
Nerve Tissue Proteins
Nkx2-2 protein, mouse
Olig2 protein, mouse
Oligodendrocyte Transcription Factor 2
Proteoglycans
RNA, Messenger
SOX9 Transcription Factor
Sox9 protein, mouse
Transcription Factors
chondroitin sulfate proteoglycan 4
ganglioside A2B5
Receptor, Platelet-Derived Growth Factor alpha