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成熟和未成熟嗅觉感觉神经元的基因组学。

Genomics of mature and immature olfactory sensory neurons.

机构信息

Department of Physiology, University of Kentucky, Lexington, Kentucky 40536-0298, USA.

出版信息

J Comp Neurol. 2012 Aug 15;520(12):2608-29. doi: 10.1002/cne.23052.

Abstract

The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of >300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein transport, RNA processing, cholesterol biosynthesis, and apoptosis via death domain receptors, were overrepresented biological processes in immature OSNs. Ion transport (ion channels), presynaptic functions, and cilia-specific processes were overrepresented in mature OSNs. Processes overrepresented among the genes expressed by all OSNs were protein and ion transport, ER overload response, protein catabolism, and the electron transport chain. To more accurately represent gradations in mRNA abundance and identify all genes expressed in each cell type, classification methods were used to produce probabilities of expression in each cell type for every gene. These probabilities, which identified 9,300 genes expressed in OSNs, were 96% accurate at identifying genes expressed in OSNs and 86% accurate at discriminating genes specific to mature and immature OSNs. This OSN gene database not only predicts the genes responsible for the major biological processes active in OSNs, but also identifies thousands of never before studied genes that support OSN phenotypes.

摘要

嗅上皮中神经元的持续替换为研究神经元分化和成熟提供了一个有利的模型。通过计算在成熟的小鼠嗅觉感觉神经元(OSN)、未成熟的 OSN 和相邻细胞类型的剩余群体样本中检测到的每个 mRNA 的相对丰度,然后将这些比率与已知的 >300 个基因的表达模式进行比较,确定了能够准确预测几乎所有基因 OSN 表达模式的富集标准。我们鉴定了 847 个未成熟 OSN 特异性和 691 个成熟 OSN 特异性基因。染色质修饰和转录因子对基因表达的控制,以及通过死亡域受体的神经元突生长、蛋白质运输、RNA 处理、胆固醇生物合成和细胞凋亡,在未成熟的 OSN 中是过度表达的生物学过程。离子转运(离子通道)、突触前功能和纤毛特异性过程在成熟的 OSN 中过度表达。在所有 OSN 表达的基因中,过度表达的过程包括蛋白质和离子转运、内质网过载反应、蛋白质分解代谢和电子传递链。为了更准确地表示 mRNA 丰度的梯度,并鉴定每种细胞类型中表达的所有基因,使用分类方法为每个基因在每种细胞类型中的表达产生表达概率。这些概率确定了 9300 个在 OSN 中表达的基因,在识别 OSN 中表达的基因时准确率为 96%,在区分成熟和未成熟 OSN 特异性基因时准确率为 86%。这个 OSN 基因数据库不仅预测了负责 OSN 中主要生物过程的基因,还鉴定了数千个以前从未研究过的基因,这些基因支持 OSN 表型。

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