Abstract
Neural stem/progenitor cells have self-renewal and multi-lineage potential. Spontaneous differentiation into neurons and glial cells occurs when neural progenitor cells are isolated from fetal or adult mammalian brain and cultured in absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF). We examined the characteristics of spontaneous differentiation and the effect of exogenous CNTF on the cell fate determination in cultured adult rat hippocampal progenitor cells (AHPs). Exogenous CNTF was found to strongly induce AHPs to differentiate into both neurons and glial cells, which are the same cell types that result from the spontaneous differentiation. Quantitative RT-PCR and immunochemical staining revealed that the 4th passage or multiple passages (22nd passages) of AHPs expressed high levels of endogenous CNTF. A neutralizing antibody against CNTF alleviated the spontaneous neuronal and glial differentiation of AHPs. FGF-2 dramatically inhibited the spontaneous differentiation and down-regulated the expression level of endogenous CNTF dose-dependently. These results suggest that the spontaneous differentiation of AHPs is mediated partially by endogenous CNTF and counteracted by FGF-2 through negative regulation of the production of endogenous CNTF in AHPs.
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