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

Mineto Ota; Yasuo Nagafuchi; Hiroaki Hatano; Kazuyoshi Ishigaki; Chikashi Terao; Yusuke Takeshima; Haruyuki Yanaoka; Satomi Kobayashi; Mai Okubo; Harumi Shirai; Yusuke Sugimori; Junko Maeda; Masahiro Nakano; Saeko Yamada; Ryochi Yoshida; Haruka Tsuchiya; Yumi Tsuchida; Shuji Akizuki; Hajime Yoshifuji; Koichiro Ohmura; Tsuneyo Mimori; Ken Yoshida; Daitaro Kurosaka; Masato Okada; Keigo Setoguchi; Hiroshi Kaneko; Nobuhiro Ban; Nami Yabuki; Kosuke Matsuki; Hironori Mutoh; Sohei Oyama; Makoto Okazaki; Hiroyuki Tsunoda; Yukiko Iwasaki; Shuji Sumitomo; Hirofumi Shoda; Yuta Kochi; Yukinori Okada; Kazuhiko Yamamoto; Tomohisa Okamura; Keishi Fujio

doi:10.1016/j.cell.2021.03.056

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

Mineto Ota, Yasuo Nagafuchi, Hiroaki Hatano, Kazuyoshi Ishigaki, Chikashi Terao, Yusuke Takeshima, Haruyuki Yanaoka, Satomi Kobayashi, Mai Okubo, Harumi Shirai, Yusuke Sugimori, Junko Maeda, Masahiro Nakano, Saeko Yamada, Ryochi Yoshida, Haruka Tsuchiya, Yumi Tsuchida, Shuji Akizuki, Hajime Yoshifuji, Koichiro OhmuraTsuneyo Mimori, Ken Yoshida, Daitaro Kurosaka, Masato Okada, Keigo Setoguchi, Hiroshi Kaneko, Nobuhiro Ban, Nami Yabuki, Kosuke Matsuki, Hironori Mutoh, Sohei Oyama, Makoto Okazaki, Hiroyuki Tsunoda, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Yuta Kochi, Yukinori Okada, Kazuhiko Yamamoto, Tomohisa Okamura, Keishi Fujio

研究成果: Article › 査読

132 被引用数 (Scopus)

抄録

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.

本文言語	English
ページ（範囲）	3006-3021.e17
ジャーナル	Cell
巻	184
号	11
DOI	https://doi.org/10.1016/j.cell.2021.03.056
出版ステータス	Published - 2021 5月 27
外部発表	はい

ASJC Scopus subject areas

生化学、遺伝学、分子生物学一般

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10.1016/j.cell.2021.03.056

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引用スタイル

Ota, M., Nagafuchi, Y., Hatano, H., Ishigaki, K., Terao, C., Takeshima, Y., Yanaoka, H., Kobayashi, S., Okubo, M., Shirai, H., Sugimori, Y., Maeda, J., Nakano, M., Yamada, S., Yoshida, R., Tsuchiya, H., Tsuchida, Y., Akizuki, S., Yoshifuji, H., ... Fujio, K. (2021). Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases. Cell, 184(11), 3006-3021.e17. https://doi.org/10.1016/j.cell.2021.03.056

Ota, M, Nagafuchi, Y, Hatano, H, Ishigaki, K, Terao, C, Takeshima, Y, Yanaoka, H, Kobayashi, S, Okubo, M, Shirai, H, Sugimori, Y, Maeda, J, Nakano, M, Yamada, S, Yoshida, R, Tsuchiya, H, Tsuchida, Y, Akizuki, S, Yoshifuji, H, Ohmura, K, Mimori, T, Yoshida, K, Kurosaka, D, Okada, M, Setoguchi, K, Kaneko, H, Ban, N, Yabuki, N, Matsuki, K, Mutoh, H, Oyama, S, Okazaki, M, Tsunoda, H, Iwasaki, Y, Sumitomo, S, Shoda, H, Kochi, Y, Okada, Y, Yamamoto, K, Okamura, T & Fujio, K 2021, 'Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases', Cell, vol. 184, no. 11, pp. 3006-3021.e17. https://doi.org/10.1016/j.cell.2021.03.056

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abstract = "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.",

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AU - Takeshima, Yusuke

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AU - Tsuchiya, Haruka

AU - Tsuchida, Yumi

AU - Akizuki, Shuji

AU - Yoshifuji, Hajime

AU - Ohmura, Koichiro

AU - Mimori, Tsuneyo

AU - Yoshida, Ken

AU - Kurosaka, Daitaro

AU - Okada, Masato

AU - Setoguchi, Keigo

AU - Kaneko, Hiroshi

AU - Ban, Nobuhiro

AU - Yabuki, Nami

AU - Matsuki, Kosuke

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AU - Oyama, Sohei

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AU - Iwasaki, Yukiko

AU - Sumitomo, Shuji

AU - Shoda, Hirofumi

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

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