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通过高通量RNA测序获得的胚胎和新生小鼠皮质转录组

Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing.

作者信息

Han Xinwei, Wu Xia, Chung Wen-Yu, Li Tao, Nekrutenko Anton, Altman Naomi S, Chen Gong, Ma Hong

机构信息

Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.

出版信息

Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12741-6. doi: 10.1073/pnas.0902417106. Epub 2009 Jul 17.

Abstract

Brain structure and function experience dramatic changes from embryonic to postnatal development. Microarray analyses have detected differential gene expression at different stages and in disease models, but gene expression information during early brain development is limited. We have generated >27 million reads to identify mRNAs from the mouse cortex for >16,000 genes at either embryonic day 18 (E18) or postnatal day 7 (P7), a period of significant synaptogenesis for neural circuit formation. In addition, we devised strategies to detect alternative splice forms and uncovered more splice variants. We observed differential expression of 3,758 genes between the 2 stages, many with known functions or predicted to be important for neural development. Neurogenesis-related genes, such as those encoding Sox4, Sox11, and zinc-finger proteins, were more highly expressed at E18 than at P7. In contrast, the genes encoding synaptic proteins such as synaptotagmin, complexin 2, and syntaxin were up-regulated from E18 to P7. We also found that several neurological disorder-related genes were highly expressed at E18. Our transcriptome analysis may serve as a blueprint for gene expression pattern and provide functional clues of previously unknown genes and disease-related genes during early brain development.

摘要

从胚胎期到出生后发育阶段,大脑结构和功能经历了显著变化。微阵列分析已在不同阶段和疾病模型中检测到差异基因表达,但早期大脑发育过程中的基因表达信息有限。我们已生成超过2700万条读数,以鉴定胚胎第18天(E18)或出生后第7天(P7)时来自小鼠皮层的16000多个基因的mRNA,这是神经回路形成过程中突触大量生成的时期。此外,我们设计了检测可变剪接形式的策略,并发现了更多的剪接变体。我们观察到这两个阶段之间有3758个基因存在差异表达,其中许多基因具有已知功能或预计对神经发育很重要。与神经发生相关的基因,如编码Sox4、Sox11和锌指蛋白的基因,在E18时比在P7时表达更高。相反,编码突触蛋白如突触结合蛋白、复合体2和突触融合蛋白的基因从E18到P7上调。我们还发现,一些与神经系统疾病相关的基因在E18时高表达。我们的转录组分析可作为基因表达模式的蓝图,并为早期大脑发育过程中先前未知基因和疾病相关基因的功能提供线索。

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