Easterday Mathew C, Dougherty Joseph D, Jackson Robert L, Ou Jing, Nakano Ichiro, Paucar Andres A, Roobini Babak, Dianati Mehrnoosh, Irvin Dwain K, Weissman Irving L, Terskikh Alexey V, Geschwind Daniel H, Kornblum Harley I
Interdepartmental Program for Neuroscience, UCLA, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Dev Biol. 2003 Dec 15;264(2):309-22. doi: 10.1016/j.ydbio.2003.09.003.
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 hematopoietic 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.
鉴定调控神经祖细胞（NPC）功能的基因对于发育神经科学和神经修复至关重要。此前，我们结合基因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。在此，我们应用一种策略进一步对神经祖细胞基因进行分层。原位杂交显示，如此鉴定出的54个克隆在中枢神经系统生发区表达，这使得它们与脑和神经祖细胞发育的研究高度相关。利用微阵列分析，我们发现73个基因在不同条件下生成的三个含神经干细胞（NSC）群体中富集。我们使用定制微阵列鉴定出38个“干性”基因，它们在三种NSC条件下表达富集，且存在于胚胎干细胞和造血干细胞中。然而，对这些干细胞群体表达谱的比较表明，虽然存在共享基因表达，但基因重叠量不超过随机预期值，这表明不同干细胞具有很大不同的基因表达模式。综上所述，这些研究鉴定出许多先前未与神经祖细胞生物学相关联的基因，并且还为用于功能分析的微阵列数据分层提供了合理方案。
