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タイトル: | A multi-omic analysis of human naïve CD4+ T cells |
著者: | Mitchell, Christopher J. Getnet, Derese Kim, Min Sik Manda, Srikanth S. Kumar, Praveen Huang, Tai Chung Pinto, Sneha M. Nirujogi, Raja Sekhar Iwasaki, Mio https://orcid.org/0000-0003-2085-732X (unconfirmed) Shaw, Patrick G. Wu, Xinyan Zhong, Jun Chaerkady, Raghothama Marimuthu, Arivusudar Muthusamy, Babylakshmi Sahasrabuddhe, Nandini A. Raju, Rajesh Bowman, Caitlyn Danilova, Ludmila Cutler, Jevon Kelkar, Dhanashree S. Drake, Charles G. Prasad, T. S Keshava Marchionni, Luigi Murakami, Peter N. Scott, Alan F. Shi, Leming Thierry-Mieg, Jean Thierry-Mieg, Danielle Irizarry, Rafael Cope, Leslie Ishihama, Yasushi https://orcid.org/0000-0001-7714-203X (unconfirmed) Wang, Charles Gowda, Harsha Pandey, Akhilesh |
著者名の別形: | 石濱, 泰 |
キーワード: | Whole genome sequencing Epigenomics Transcriptomics Proteomics Phosphoproteomics Integrative -omics Innate immunity |
発行日: | 6-Nov-2015 |
出版者: | BioMed Central Ltd. |
誌名: | BMC Systems Biology |
巻: | 9 |
論文番号: | 75 |
抄録: | Background: 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. Results: 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. Conclusions: 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. |
著作権等: | © 2015 Mitchell et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
URI: | http://hdl.handle.net/2433/210426 |
DOI(出版社版): | 10.1186/s12918-015-0225-4 |
PubMed ID: | 26542228 |
出現コレクション: | 学術雑誌掲載論文等 |
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