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

Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing
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DOI:
10.1073/pnas.0902417106
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发表时间:
2009-08-04
影响因子:
11.1
通讯作者:
Ma, Hong
Ma, Hong
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Han, Xinwei;Wu, Xia;Ma, Hong

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从胚胎到出生后,大脑的结构和功能经历了巨大的变化。微阵列分析已经检测到不同阶段和疾病模型中的差异基因表达,但早期脑发育过程中的基因表达信息有限。我们已经产生了> 2700万个读段,以在胚胎第18天(E18)或出生后第7天(P7)识别来自小鼠皮层的> 16,000个基因的mRNA,这是神经回路形成的重要突触发生时期。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。我们观察到两个阶段之间有3,758个基因的差异表达,其中许多基因具有已知的功能或预测对神经发育很重要。神经发生相关基因,如编码Sox4,Sox11和锌指蛋白的基因,在E18比P7表达更高。相反,编码突触蛋白的基因,如synaptotagmin,complexin 2,syntaxin从E18到P7上调。我们还发现,一些神经系统疾病相关的基因在E18高度表达。我们的转录组分析可以作为基因表达模式的蓝图,并提供以前未知的基因和疾病相关基因在早期脑发育过程中的功能线索。
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 synapto-genesis 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.