Analysis of the Expression and Function of BRINP Family Genes During Neuronal Differentiation in Mouse Embryonic Stem Cell-Derived Neural Stem Cells
Analysis of the Expression and Function of BRINP Family Genes During Neuronal Differentiation in Mouse Embryonic Stem Cell-Derived Neural Stem Cells
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DOI：
10.1002/jnr.22315
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发表时间：
2010-05-15
影响因子：
4.2
通讯作者：
Matsuoka, Ichiro
中科院分区：
文献类型：
--
作者：
Terashima, Michiyo;Kobayashi, Miwako;Matsuoka, Ichiro
我们以前发现了一个新的基因家族，BRINP1、2和3，它们在中枢神经系统(CNS)和外周神经系统(PNS)中都广泛表达。在本研究中，我们分析了三个BRINP基因在小鼠胚胎干细胞(ES)来源的神经干细胞(NSCs)分化过程中的表达模式及其对NSCs细胞周期调控的影响。在小鼠ES细胞中未见BRINP-mRNAs的表达，而在ES细胞来源的神经干细胞中高水平表达BRINP-1和2-mRNAs。在维甲酸和脑源性神经营养因子的诱导下，三种类型的BRINP-mRNA均被诱导成神经细胞，其诱导过程相似，在处理的第3天达到高峰。在有血清存在的条件下，星形胶质细胞分化为星形胶质细胞后，BRINP1-mRNA表达略有上调，而BRINP2-和BRINP3-mRNAs几乎消失。在指数生长期的神经干细胞群体中，分别有69.2%、26.1%和7.7%的细胞处于G1期、S期和G2期，而三个BRINP基因中的任何一个过表达都能完全消除G2期的细胞，并使S期的细胞显著减少到11.8%~13.8%。基于这些结果，讨论了诱导的BRINP基因在终末分化的有丝分裂后神经元细胞周期抑制中的生理作用。(C)2009年Wiley-Liss，Inc.
We previously identified a novel family of genes, BRINP1, 2, and 3, that are predominantly and widely expressed in both the central nervous system (CNS) and peripheral nervous system (PNS). In the present study, we analyzed the expression pattern of three BRINP genes during differentiation of mouse embryonic stem (ES) cell-derived neural stem cells (NSCs) and their effects on the cell-cycle regulation of NSCs. While there was no significant expression of any BRINP-mRNA expressed in mouse ES cells, BRINP 1 and 2-mRNAs was expressed at high levels in the ES cell-derived neural stem cells. Upon differentiation into neuronal cells in the presence of retinoic acid and BDNF, all three types of BRINP-mRNA were induced with a similar time course peaking at day three of treatment. Upon differentiation into astroglial cells in the presence of serum, BRINP1-mRNA was slightly up-regulated, while BRINP2- and BRINP3-mRNAs were almost abolished in the astrocytes. While 69.2, 26.1, and 7.7% of cells in a population of NSCs in the exponentially growing phase were in the G1, S and G2 phases, respectively, over-expression of any one of the three BRINP genes completely abolished cells in the G2 phase and significantly reduced the cells in S phase to 11.8-13.8%. Based on these results, the physiological roles of induced BRINP genes in the cell-cycle suppression of terminally differentiated post-mitotic neurons are discussed. (C) 2009 Wiley-Liss, Inc.