Functional genomics identifies neural stem cell sub-type expression profiles and genes regulating neuroblast homeostasis
Functional genomics identifies neural stem cell sub-type expression profiles and genes regulating neuroblast homeostasis
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DOI：
10.1016/j.ydbio.2011.10.020
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发表时间：
2012-01-01
影响因子：
2.7
通讯作者：
Doe, Chris Q.
中科院分区：
文献类型：
--
作者：
Carney, Travis D.;Miller, Michael R.;Doe, Chris Q.
果蝇幼虫的中枢脑包含约10000个分化的神经元和200个分散的神经祖细胞（神经母细胞），每个脑叶可进一步细分为约95个I型神经母细胞和8个II型神经母细胞。只有II型神经母细胞产生自我更新的中间神经祖细胞（INPs），因此每个II型神经母细胞对脑贡献更多的神经元，包括大部分的中央复合体。我们描述了六种不同的突变基因型，它们导致神经母细胞数量增加；有些优先使II型或I型神经母细胞扩增。将这些突变基因型的幼虫脑与野生型进行转录谱分析，使我们能够识别在II型或I型神经母细胞中富集的小转录本簇，并且我们通过基因表达分析验证了这些簇。出乎意料的是，发现I型/II型神经母细胞之间差异表达的基因很少，这表明这些基因在建立不同细胞类型中起重要作用。我们还鉴定了一大组预计在所有神经母细胞中表达但不在神经元中表达的基因。我们进行了基于神经母细胞特异性RNA干扰的功能筛选，并鉴定出84个维持适当神经母细胞数量所必需的基因：所有这些基因都有保守的哺乳动物直系同源物。这些基因是调节果蝇和哺乳动物神经祖细胞自我更新的极佳候选基因。（C）2011爱思唯尔公司。保留所有权利。
The Drosophila larval central brain contains about 10,000 differentiated neurons and 200 scattered neural progenitors (neuroblasts), which can be further subdivided into similar to 95 type I neuroblasts and eight type II neuroblasts per brain lobe. Only type II neuroblasts generate self-renewing intermediate neural progenitors (INPs), and consequently each contributes more neurons to the brain, including much of the central complex. We characterized six different mutant genotypes that lead to expansion of neuroblast numbers; some preferentially expand type II or type I neuroblasts. Transcriptional profiling of larval brains from these mutant genotypes versus wild-type allowed us to identify small clusters of transcripts enriched in type II or type I neuroblasts, and we validated these clusters by gene expression analysis. Unexpectedly, only a few genes were found to be differentially expressed between type I/II neuroblasts, suggesting that these genes play a large role in establishing the different cell types. We also identified a large group of genes predicted to be expressed in all neuroblasts but not in neurons. We performed a neuroblast-specific, RNAi-based functional screen and identified 84 genes that are required to maintain proper neuroblast numbers: all have conserved mammalian orthologs. These genes are excellent candidates for regulating neural progenitor self-renewal in Drosophila and mammals. (C) 2011 Elsevier Inc. All rights reserved.