Lee Don-Ching, Hsu Yi-Chao, Chung Yu-Fen, Hsiao Chao-Yang, Chen Su-Liang, Chen Mei-Shu, Lin Hua-Kuo, Chiu Ing-Ming
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan, ROC.
Mol Cell Neurosci. 2009 Jul;41(3):348-63. doi: 10.1016/j.mcn.2009.04.010. Epub 2009 May 3.
Fibroblast growth factor 1 (FGF1) and FGF2 have been shown to maintain the proliferation, self-renewal and multipotent capacities of neural stem/progenitor cells (NSPCs) in vitro. FGF1 is unique for binding to all known FGF receptors. In this study, we investigated if exogenous EGF and FGF1 could be used in the isolation of NSPCs from embryonic mouse brains. We demonstrated that EGF/FGF1-responsive cells exhibited lower proliferation rate and neurosphere formation efficiency than EGF/FGF2-responsive NSPCs. However, EGF/FGF1-responsive mouse brain cells exhibited better neural differentiation capacities than EGF/FGF2-responsive NSPCs at E11.5. Using F1BGFP reporter, we further demonstrated that F1BGFP+ cells showed similar multipotent capacities to CD133+ NSPCs, and could be induced more efficiently toward neuronal differentiation. Our results suggested that EGF/FGF1-responsive cells from E11.5 mouse brains could self-renew and have better multipotency than EGF/FGF2-responsive NSPCs. Further, CD133+ and F1BGFP+ NSPCs may also represent different subsets of NSPCs during neural development and adult neurogenesis.
成纤维细胞生长因子1(FGF1)和FGF2已被证明在体外可维持神经干/祖细胞(NSPCs)的增殖、自我更新和多能性。FGF1对于与所有已知的FGF受体结合而言是独特的。在本研究中,我们调查了外源性表皮生长因子(EGF)和FGF1是否可用于从胚胎小鼠大脑中分离NSPCs。我们证明,与对EGF/FGF2有反应的NSPCs相比,对EGF/FGF1有反应的细胞表现出更低的增殖率和神经球形成效率。然而,在胚胎期11.5天(E11.5)时,对EGF/FGF1有反应的小鼠脑细胞比对应EGF/FGF2的NSPCs表现出更好的神经分化能力。使用F1BGFP报告基因,我们进一步证明F1BGFP+细胞表现出与CD133+ NSPCs相似的多能性,并且可以更有效地被诱导向神经元分化。我们的结果表明,来自E11.5小鼠大脑的对EGF/FGF1有反应的细胞能够自我更新,并且比对应EGF/FGF2的NSPCs具有更好的多能性。此外,在神经发育和成年神经发生过程中,CD133+和F1BGFP+ NSPCs可能也代表了NSPCs的不同亚群。