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Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases

Cell, 2021-05, Vol.184 (11), p.3006-3021.e17 [Peer Reviewed Journal]

2021 Elsevier Inc. ;Copyright © 2021 Elsevier Inc. All rights reserved. ;ISSN: 0092-8674 ;EISSN: 1097-4172 ;DOI: 10.1016/j.cell.2021.03.056 ;PMID: 33930287

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Title:
Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases
Author: Ota, Mineto ; Nagafuchi, Yasuo ; Hatano, Hiroaki ; Ishigaki, Kazuyoshi ; Terao, Chikashi ; Takeshima, Yusuke ; Yanaoka, Haruyuki ; Kobayashi, Satomi ; Okubo, Mai ; Shirai, Harumi ; Sugimori, Yusuke ; Maeda, Junko ; Nakano, Masahiro ; Yamada, Saeko ; Yoshida, Ryochi ; Tsuchiya, Haruka ; Tsuchida, Yumi ; Akizuki, Shuji ; Yoshifuji, Hajime ; Ohmura, Koichiro ; Mimori, Tsuneyo ; Yoshida, Ken ; Kurosaka, Daitaro ; Okada, Masato ; Setoguchi, Keigo ; Kaneko, Hiroshi ; Ban, Nobuhiro ; Yabuki, Nami ; Matsuki, Kosuke ; Mutoh, Hironori ; Oyama, Sohei ; Okazaki, Makoto ; Tsunoda, Hiroyuki ; Iwasaki, Yukiko ; Sumitomo, Shuji ; Shoda, Hirofumi ; Kochi, Yuta ; Okada, Yukinori ; Yamamoto, Kazuhiko ; Okamura, Tomohisa ; Fujio, Keishi
Subjects: Adult ; cell-type-specific eQTL ; context-dependent eQTL ; expression quantitative trait loci ; Female ; Gene Expression - genetics ; Gene Expression - immunology ; Gene Expression Regulation - genetics ; Gene Expression Regulation - immunology ; gene regulation ; Genetic Predisposition to Disease - genetics ; Genome-Wide Association Study - methods ; Humans ; immune cell ; Immune Cell Gene Expression Atlas from the University of Tokyo ; Immune System - cytology ; Immune System - metabolism ; Immune System Diseases - genetics ; Immune System Diseases - metabolism ; Immune System Diseases - physiopathology ; immune-mediated disease ; immunogenetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide - genetics ; Quantitative Trait Loci - genetics ; Quantitative Trait Loci - immunology ; systemic lupus erythematosus ; transcriptome ; Transcriptome - genetics ; Whole Genome Sequencing - methods
Is Part Of: Cell, 2021-05, Vol.184 (11), p.3006-3021.e17
Description: Genetic studies have revealed many variant loci that are associated with immune-mediated diseases. To elucidate the disease pathogenesis, it is essential to understand the function of these variants, especially under disease-associated conditions. Here, we performed a large-scale immune cell gene-expression analysis, together with whole-genome sequence analysis. Our dataset consists of 28 distinct immune cell subsets from 337 patients diagnosed with 10 categories of immune-mediated diseases and 79 healthy volunteers. Our dataset captured distinctive gene-expression profiles across immune cell types and diseases. Expression quantitative trait loci (eQTL) analysis revealed dynamic variations of eQTL effects in the context of immunological conditions, as well as cell types. These cell-type-specific and context-dependent eQTLs showed significant enrichment in immune disease-associated genetic variants, and they implicated the disease-relevant cell types, genes, and environment. This atlas deepens our understanding of the immunogenetic functions of disease-associated variants under in vivo disease conditions. [Display omitted] •Gene-regulation atlas of 28 immune cell types under immune-mediated diseases (IMDs)•Expression QTLs show immune cell-type and disease context specificity•Cellular pathways diversify eQTL effects under in vivo disease conditions•This atlas links IMD GWAS variants to susceptible genes, cell types, and environment The gene-regulation atlas of 28 immune cell types was constructed with immune-mediated disease patient samples and shows the dynamics of gene regulation depending on cell types and immunological conditions.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0092-8674
EISSN: 1097-4172
DOI: 10.1016/j.cell.2021.03.056
PMID: 33930287
Source: Cell Press Free Archives
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Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases

2021 Elsevier Inc. ;Copyright © 2021 Elsevier Inc. All rights reserved. ;ISSN: 0092-8674 ;EISSN: 1097-4172 ;DOI: 10.1016/j.cell.2021.03.056 ;PMID: 33930287

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