Neural progenitor genes - Germinal zone expression and analysis of genetic overlap in stem cell populations

Neural progenitor genes - Germinal zone expression and analysis of genetic overlap in stem cell populations
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DOI:
10.1016/j.ydbio.2003.09.003
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发表时间:
2003-12-15
影响因子:
2.7
通讯作者:
Kornblum, HI
Kornblum, HI
中科院分区:
生物学3区
文献类型:
--
作者:
Easterday, MC;Dougherty, JD;Kornblum, HI

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调节神经祖细胞(NPC)功能的基因的鉴定对于发育神经科学和神经修复具有重要意义。此前,我们结合遗传消减和微阵列分析来鉴定神经祖细胞培养物中富集的基因。在这里,我们应用一种策略来进一步对神经祖基因进行分层。原位杂交证明了如此鉴定的 54 个克隆在中枢神经系统生发区的表达,使它们与大脑和神经祖细胞发育研究高度相关。通过微阵列分析,我们发现在不同条件下产生的三个含有神经干细胞 (NSC) 的群体中富集了 73 个基因。我们使用定制微阵列来鉴定 38 个“干性”基因,这些基因在三种 NSC 条件下表达丰富,并且存在于胚胎干细胞和造血干细胞中。然而,对这些干细胞群表达谱的比较表明,虽然存在共享的基因表达,但遗传重叠的数量并不比偶然预期的多,这表明不同的干细胞具有很大不同的基因表达模式。总而言之,这些研究鉴定了许多以前与神经祖细胞生物学无关的基因,并为功能分析的微阵列数据分层提供了合理的方案。 (C) 2003 Elsevier Inc. 保留所有权利。
The identification of the genes regulating neural progenitor cell (NPC) functions is of great importance to developmental neuroscience and neural repair. Previously, we combined genetic subtraction and microarray analysis to identify genes enriched in neural progenitor cultures. Here, we apply a strategy to further stratify the neural progenitor genes. In situ hybridization demonstrates expression in the central nervous system germinal zones of 54 clones so identified, making them highly relevant for study in brain and neural progenitor development. Using microarray analysis we find 73 genes enriched in three neural stem cell (NSC)-containing populations generated under different conditions. We use the custom microarray to identify 38 "stemness" genes, with enriched expression in the three NSC conditions and present in both embryonic stem cells and hernatopoietic stem cells. However, comparison of expression profiles from these stem cell populations indicates that while there is shared gene expression, the amount of genetic overlap is no more than what would be expected by chance, indicating that different stem cells have largely different gene expression patterns. Taken together, these studies identify many genes not previously associated with neural progenitor cell biology and also provide a rational scheme for stratification of microarray data for functional analysis. (C) 2003 Elsevier Inc. All fights reserved.