A multi-omic analysis of human naïve CD4+ T cells.
A multi-omic analysis of human naïve CD4+ T cells.
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DOI：
10.1186/s12918-015-0225-4
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发表时间：
2015-11-06
影响因子：
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通讯作者：
Pandey A
中科院分区：
文献类型：
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作者：
Mitchell CJ;Getnet D;Kim MS;Manda SS;Kumar P;Huang TC;Pinto SM;Nirujogi RS;Iwasaki M;Shaw PG;Wu X;Zhong J;Chaerkady R;Marimuthu A;Muthusamy B;Sahasrabuddhe NA;Raju R;Bowman C;Danilova L;Cutler J;Kelkar DS;Drake CG;Prasad TS;Marchionni L;Murakami PN;Scott AF;Shi L;Thierry-Mieg J;Thierry-Mieg D;Irizarry R;Cope L;Ishihama Y;Wang C;Gowda H;Pandey A
细胞功能和多样性是由基本生物分子（包括DNA、RNA和蛋白质）的复杂相互作用协调的。基因组学、表观基因组学、转录组学和蛋白质组学的技术进步使得能够进行大规模平行和无偏倚的测量。这种高通量技术已被广泛用于开展广泛的、无偏见的研究，特别是在人类疾病方面。然而，尚未对单一人类细胞类型的基因组、表观基因组、转录组和蛋白质组进行统一分析，以获得各种生物分子之间复杂相互作用的连贯观点。在这里，我们报告了从单个个体中分离的人原代幼稚CD 4 + T细胞的第一个多组学分析。整合多组学数据集使我们能够研究全基因组甲基化及其对mRNA/蛋白质表达模式的影响，正常生理条件下RNA编辑的程度以及幼稚CD 4 + T细胞中的等位基因特异性表达。此外，我们进行了幼稚与初级静息记忆CD 4 + T细胞的多组学比较分析，以确定T细胞分化的分子变化。该分析提供了关于参与T细胞受体信号传导的几种分子如何在DNA、RNA和蛋白质水平上调节的机制见解。磷酸化蛋白质组学揭示了调节这两种细胞状态的下游信号传导事件。来自相同遗传背景的多组学数据的可用性也使我们能够采用新的蛋白质基因组学方法来识别人类基因组中的个体特异性变体和推定的新蛋白质编码区。我们利用多种高通量技术从单个供体中获得两种主要人类细胞类型的综合概况，即幼稚CD 4 + T细胞和记忆CD 4 + T细胞。通过全基因组测序、甲基化阵列、RNA-Seq、miRNA-Seq、蛋白质组学和磷酸蛋白质组学的垂直和水平整合，我们获得了这两种密切相关的免疫细胞的整合和比较图谱，并确定了抗原接触后免疫细胞分化的潜在分子效应物。本文的在线版本（doi：10.1186/s12918-015-0225-4）包含补充材料，可供授权用户使用。
Cellular function and diversity are orchestrated by complex interactions of fundamental biomolecules including DNA, RNA and proteins. Technological advances in genomics, epigenomics, transcriptomics and proteomics have enabled massively parallel and unbiased measurements. Such high-throughput technologies have been extensively used to carry out broad, unbiased studies, particularly in the context of human diseases. Nevertheless, a unified analysis of the genome, epigenome, transcriptome and proteome of a single human cell type to obtain a coherent view of the complex interplay between various biomolecules has not yet been undertaken. Here, we report the first multi-omic analysis of human primary naïve CD4+ T cells isolated from a single individual. Integrating multi-omics datasets allowed us to investigate genome-wide methylation and its effect on mRNA/protein expression patterns, extent of RNA editing under normal physiological conditions and allele specific expression in naïve CD4+ T cells. In addition, we carried out a multi-omic comparative analysis of naïve with primary resting memory CD4+ T cells to identify molecular changes underlying T cell differentiation. This analysis provided mechanistic insights into how several molecules involved in T cell receptor signaling are regulated at the DNA, RNA and protein levels. Phosphoproteomics revealed downstream signaling events that regulate these two cellular states. Availability of multi-omics data from an identical genetic background also allowed us to employ novel proteogenomics approaches to identify individual-specific variants and putative novel protein coding regions in the human genome. We utilized multiple high-throughput technologies to derive a comprehensive profile of two primary human cell types, naïve CD4+ T cells and memory CD4+ T cells, from a single donor. Through vertical as well as horizontal integration of whole genome sequencing, methylation arrays, RNA-Seq, miRNA-Seq, proteomics, and phosphoproteomics, we derived an integrated and comparative map of these two closely related immune cells and identified potential molecular effectors of immune cell differentiation following antigen encounter. The online version of this article (doi:10.1186/s12918-015-0225-4) contains supplementary material, which is available to authorized users.