Gene amplification during differentiation of mammalian neural stem cells in vitro and in vivo
Gene amplification during differentiation of mammalian neural stem cells in vitro and in vivo
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DOI：
10.18632/oncotarget.3248
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发表时间：
2015-03-30
期刊：
影响因子：
--
通讯作者：
Meese, Eckart
中科院分区：
文献类型：
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作者：
Fischer, Ulrike;Backes, Christina;Meese, Eckart
在两栖动物和果蝇的发育过程中，基因扩增是增加基因表达的机制之一。在哺乳动物细胞中，基因扩增似乎仅限于肿瘤发生和癌细胞耐药的获得。在这里，我们报告了小鼠神经祖细胞在分化过程中一个复杂的基因扩增模式，涉及大约10%的基因组。半数扩增的小鼠染色体区域与先前在人类神经祖细胞中报道的扩增区域重叠，表明分化过程中的保守机制。利用荧光原位杂交技术，对小鼠中脑E14（胚胎期）原代神经球细胞分化过程中的单细胞扩增进行了验证。在体内，我们在E11.5期小鼠胚胎的冷冻切片中证实了TRP53基因的基因扩增。基因扩增不仅是一种与癌症相关的机制，而且在进化中也是保守的，发生在哺乳动物神经干细胞的分化过程中
In development of amphibians and flies, gene amplification is one of mechanisms to increase gene expression. In mammalian cells, gene amplification seems to be restricted to tumorigenesis and acquiring of drug-resistance in cancer cells. Here, we report a complex gene amplification pattern in mouse neural progenitor cells during differentiation with approximately 10% of the genome involved. Half of the amplified mouse chromosome regions overlap with amplified regions previously reported in human neural progenitor cells, indicating conserved mechanisms during differentiation. Using fluorescence in situ hybridization, we verified the amplification in single cells of primary mouse mesencephalon E14 (embryonic stage) neurosphere cells during differentiation. In vivo we confirmed gene amplifications of the TRP53 gene in cryosections from mouse embryos at stage E11.5. Gene amplification is not only a cancer-related mechanism but is also conserved in evolution, occurring during differentiation of mammalian neural stem cells