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Establishment and characterization of a multipotential neural cell line that can conditionally generate neurons, astrocytes, and oligodendrocytes in vitro
Author(s) -
Nakafuku Masato,
Nakamura S.
Publication year - 1995
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490410203
Subject(s) - neuroepithelial cell , neurosphere , basic fibroblast growth factor , biology , microbiology and biotechnology , neural stem cell , embryonic stem cell , stem cell , fibroblast growth factor , astrocyte , cellular differentiation , epidermal growth factor , neuroscience , in vitro , cell culture , growth factor , adult stem cell , central nervous system , endothelial stem cell , genetics , receptor , gene
Abstract In the mammalian central nervous system (CNS), multipotential neural stem cells in the neuroepithelium generate the three major types of neural cells, namely, neurons, astrocytes, and oligodendrocytes. To explore the molecular mechanisms underlying proliferation and differentiation of these neural stem cells, we established a cell line named MNS‐57 from the embryonic day 12 rat neuroepithelium by introducing the mycer fusion gene, in which c‐myc can be conditionally activated by adding oestrogen to the culture medium. MNS‐57 cells expressed nestin, vimentin, and the RC1 antigen, which are potential markers for neural stem cells. We show that under particular culture conditions, MNS‐57 cells can conditionally generate neurons, astrocytes, and oligodendrocytes in vitro, indicating that they are likely to originate from multipotential neural stem cells. Incubating MNS‐57 cells with either oestrogen, which activates mycer, or growth factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) stimulated their growth, and the combination of oestrogen and bFGF (or EGF) had a synergistically stronger mitogenic effect than the single factors. Furthermore, both c‐myc activation and bFGF appeared to be necessary for the differentiation of MNS‐57 cells, and only when stimulated by both signals simultaneously, the cells committed to generating multiple neural cell types. Thus, the property of the cell line is unique in that its differentiation into neurons and glia can be conditionally manipulated invitro in an exogenous signal‐dependent manner. We propose that the cell line described here will provide an useful in vitro model to understand genetic and environmental mechanisms that control the generation of neural cell diversity in the CNS. © 1995 Wiley‐Liss, Inc.