Basic fibroblast growth factor prolongs the proliferation of rat cortical progenitor cells in vitro without altering their cell cycle parameters
Basic fibroblast growth factor prolongs the proliferation of rat cortical progenitor cells in vitro without altering their cell cycle parameters
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DOI：
10.1093/cercor/7.4.293
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发表时间：
1997-06-01
期刊：
影响因子：
3.7
通讯作者：
Parnavelas, JG
中科院分区：
文献类型：
--
作者：
Cavanagh, JFR;Mione, MC;Parnavelas, JG
碱性成纤维细胞生长因子（bFGF）已被证明影响神经系统中多种细胞类型的存活、增殖和分化。在这项调查中，我们研究了bFGF的作用：（一）增殖率;（二）细胞周期参数;（三）维持细胞分裂;（四）静止细胞的招聘;和（五）从E16大鼠胚胎制备的培养物中的皮质祖细胞的分化程度。皮质祖细胞的增殖率（标记指数）在bFGF的存在下增加了一倍，超过48小时。然而，细胞周期相的长度没有变化。体外第一天（DIV）标记有重组逆转录病毒的克隆在碱性成纤维细胞生长因子的存在下显着变大。此外，在对照培养物中检查的许多克隆在最多四个细胞周期后停止分裂，而几乎所有克隆相关细胞在bFGF存在下4天后仍在分裂，即至少六个细胞周期。碱性成纤维细胞生长因子还刺激了静止祖细胞的分裂，否则这些祖细胞将分化或经历细胞死亡。用MAP-2和GFAP免疫细胞化学方法研究5 DIV后神经元和胶质细胞的分化程度。在碱性成纤维细胞生长因子的存在下，MAP-2标记的细胞的百分比是不到一半的控制文化，而巢蛋白（祖细胞的标记物）的免疫反应性细胞的数量仍然非常高。GFAP免疫反应性细胞存在于bFGF处理的培养物中，但在对照条件下极为罕见。这些实验表明，碱性成纤维细胞生长因子，一种有效的有丝分裂原皮质祖细胞，没有影响其细胞周期的参数，但延长他们的增殖能力，促进他们的生存和延迟他们分化成神经元。
Basic fibroblast growth factor (bFGF) has been shown to influence the survival, proliferation and differentiation of a variety of cell types in the nervous system. In this investigation we have examined the action of bFGF on: (i) the rate of proliferation; (ii) cell cycle parameters; (iii) the maintenance of cell division; (iv) the recruitment of quiescent cells; and (v) the degree of differentiation of cortical progenitor cells in cultures prepared from E16 rat embryos. The proliferation rate (labelling index) of cortical progenitor cells doubled in the presence of bFGF over 48 h. However, the lengths of the cell cycle phases were unchanged. Clones marked with a recombinant retrovirus on the first day in vitro (DIV) grew significantly larger in the presence of bFGF. Furthermore, many of the clones examined in control cultures had ceased to divide after a maximum of four cell cycles, whereas almost all clonally related cells were still dividing in the presence of bFGF 4 days later, i.e. for at least six cell cycles. Basic FGF also stimulated the division of quiescent progenitor cells, which otherwise would have differentiated or undergone cell death. The degree of neuronal and glial differentiation was studied after 5 DIV using MAP-2 and GFAP immunocytochemistry. In the presence of bFGF, the percentage of MAP-2-labelled cells was less than half that of control cultures, whereas the number of cells immunoreactive for nestin (a marker of progenitor cells) remained very high. Cells immunoreactive for GFAP were present in bFGF-treated cultures, yet were extremely rare in control conditions. These experiments show that bFGF, a potent mitogen for cortical progenitor cells, has no effects on the parameters of their cell cycle but extends their proliferative capability, promotes their survival and delays their differentiation into neurons.