Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution

Edahiro, Ryuya; Sato, Go; Naito, Tatsuhiko; Shirai, Yuya; Saiki, Ryunosuke; Sonehara, Kyuto; Tomofuji, Yoshihiko; Yamamoto, Kenichi; Namba, Shinichi; Sasa, Noah; Nagao, Genta; Wang, Qingbo S.; Takahashi, Yugo; Hasegawa, Takanori; Kishikawa, Toshihiro; Suzuki, Ken; Liu, Yu Chen; Motooka, Daisuke; Takuwa, Ayako; Tanaka, Hiromu; Azekawa, Shuhei; Japan COVID-19 Task Force; Namkoong, Ho; Koike, Ryuji; Kimura, Akinori; Imoto, Seiya; Miyano, Satoru; Kanai, Takanori; Fukunaga, Koichi; Uemura, Mamoru; Morita, Takayoshi; Kato, Yasuhiro; Hirata, Haruhiko; Takeda, Yoshito; Doki, Yuichiro; Eguchi, Hidetoshi; Okuzaki, Daisuke; Sakakibara, Shuhei; Ogawa, Seishi; Kumanogoh, Atsushi; Okada, Yukinori

doi:https://doi.org/10.1038/s41588-025-02266-3

Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution

Edahiro, Ryuya; Sato, Go; Naito, Tatsuhiko et al.

Nature Genetics, 2025, 57(8), 1905-1921

アクセス数:268件（2025-12-03 09:54 集計）

固定URL: https://hdl.handle.net/11094/102930

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タイトル	Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution
著者	NRID 1000010998008 1000010998008 ORCID 0000-0001-5009-6408 0000-0001-5009-6408 researchmap permalink ryuya_edahiro_88 ryuya_edahiro_88 Scopus Author ID 56227394200 56227394200 著者名 Edahiro, Ryuya
	NRID 1000070912012 1000070912012 著者名 Sato, Go
	著者名 Naito, Tatsuhiko
	NRID 1000050899945 1000050899945 ORCID 0000-0002-0518-9020 0000-0002-0518-9020 researchmap permalink yuyashirai yuyashirai Scopus Author ID 58966287700 58966287700 著者名 Shirai, Yuya
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	著者名 Namba, Shinichi
	NRID 1000090882241 1000090882241 ORCID 0009-0008-1517-6259 0009-0008-1517-6259 researchmap permalink nsasa nsasa Scopus Author ID 57850241000 57850241000 著者名 Sasa, Noah
	著者名 Nagao, Genta
	NRID 1000000916033 1000000916033 ORCID 0000-0002-9110-5830 0000-0002-9110-5830 researchmap permalink qingbowang qingbowang 著者名 Wang, Qingbo S.
	著者名 Takahashi, Yugo
	NRID 1000080753756 1000080753756 著者名 Hasegawa, Takanori
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	著者名 Japan COVID-19 Task Force
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	NRID 1000050128104 1000050128104 著者名 Miyano, Satoru
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内容	Edahiro R., Sato G., Naito T., et al. Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution. Nature Genetics 57, 1905 (2025); https://doi.org/10.1038/s41588-025-02266-3.
抄録	Current molecular quantitative trait locus catalogs are mostly at bulk resolution and centered on Europeans. Here, we constructed an immune cell atlas with single-cell transcriptomics of >1.5 million peripheral blood mononuclear cells, host genetics, plasma proteomics and gut metagenomics from 235 Japanese persons, including patients with coronavirus disease 2019 (COVID-19) and healthy individuals. We mapped germline genetic effects on gene expression within immune cell types and across cell states. We elucidated cell type- and context-specific human leukocyte antigen (HLA) and genome-wide associations with T and B cell receptor repertoires. Colocalization using dynamic genetic regulation provided better understanding of genome-wide association signals. Differential gene and protein expression analyses depicted cell type- and context-specific effects of polygenic risks. Various somatic mutations including mosaic chromosomal alterations, loss of Y chromosome and mitochondrial DNA (mtDNA) heteroplasmy were projected into single-cell resolution. We identified immune features specific to somatically mutated cells. Overall, immune cells are dynamically regulated in a cell state-dependent manner characterized with multiomic profiles.
出版者	Nature Research
収録物名	Nature Genetics
巻(号)	57(8)
ページ	1905-1921
刊行年月	2025-07-28
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102930
PISSN	10614036
eISSN	15461718
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1038/s41588-025-02266-3
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Nature Genetics. 2025, 57(8), p. 1905-1921
DC.title	Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution
DC.creator	Edahiro, Ryuya
	Sato, Go
	Naito, Tatsuhiko
	Shirai, Yuya
	Saiki, Ryunosuke
	Sonehara, Kyuto
	Tomofuji, Yoshihiko
	Yamamoto, Kenichi
	Namba, Shinichi
	Sasa, Noah
	Nagao, Genta
	Wang, Qingbo S.
	Takahashi, Yugo
	Hasegawa, Takanori
	Kishikawa, Toshihiro
	Suzuki, Ken
	Liu, Yu Chen
	Motooka, Daisuke
	Takuwa, Ayako
	Tanaka, Hiromu
	Azekawa, Shuhei
	Japan COVID-19 Task Force
	Namkoong, Ho
	Koike, Ryuji
	Kimura, Akinori
	Imoto, Seiya
	Miyano, Satoru
	Kanai, Takanori
	Fukunaga, Koichi
	Uemura, Mamoru
	Morita, Takayoshi
	Kato, Yasuhiro
	Hirata, Haruhiko
	Takeda, Yoshito
	Doki, Yuichiro
	Eguchi, Hidetoshi
	Okuzaki, Daisuke
	Sakakibara, Shuhei
	Ogawa, Seishi
	Kumanogoh, Atsushi
	Okada, Yukinori
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-07-28
DC.identifier	https://doi.org/10.1038/s41588-025-02266-3
DC.description	Edahiro R., Sato G., Naito T., et al. Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution. Nature Genetics 57, 1905 (2025); https://doi.org/10.1038/s41588-025-02266-3.
DCTERMS.abstract	Current molecular quantitative trait locus catalogs are mostly at bulk resolution and centered on Europeans. Here, we constructed an immune cell atlas with single-cell transcriptomics of >1.5 million peripheral blood mononuclear cells, host genetics, plasma proteomics and gut metagenomics from 235 Japanese persons, including patients with coronavirus disease 2019 (COVID-19) and healthy individuals. We mapped germline genetic effects on gene expression within immune cell types and across cell states. We elucidated cell type- and context-specific human leukocyte antigen (HLA) and genome-wide associations with T and B cell receptor repertoires. Colocalization using dynamic genetic regulation provided better understanding of genome-wide association signals. Differential gene and protein expression analyses depicted cell type- and context-specific effects of polygenic risks. Various somatic mutations including mosaic chromosomal alterations, loss of Y chromosome and mitochondrial DNA (mtDNA) heteroplasmy were projected into single-cell resolution. We identified immune features specific to somatically mutated cells. Overall, immune cells are dynamically regulated in a cell state-dependent manner characterized with multiomic profiles.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	102930
citation_title	Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution
citation_author	Edahiro, Ryuya
	Sato, Go
	Naito, Tatsuhiko
	Shirai, Yuya
	Saiki, Ryunosuke
	Sonehara, Kyuto
	Tomofuji, Yoshihiko
	Yamamoto, Kenichi
	Namba, Shinichi
	Sasa, Noah
	Nagao, Genta
	Wang, Qingbo S.
	Takahashi, Yugo
	Hasegawa, Takanori
	Kishikawa, Toshihiro
	Suzuki, Ken
	Liu, Yu Chen
	Motooka, Daisuke
	Takuwa, Ayako
	Tanaka, Hiromu
	Azekawa, Shuhei
	Japan COVID-19 Task Force
	Namkoong, Ho
	Koike, Ryuji
	Kimura, Akinori
	Imoto, Seiya
	Miyano, Satoru
	Kanai, Takanori
	Fukunaga, Koichi
	Uemura, Mamoru
	Morita, Takayoshi
	Kato, Yasuhiro
	Hirata, Haruhiko
	Takeda, Yoshito
	Doki, Yuichiro
	Eguchi, Hidetoshi
	Okuzaki, Daisuke
	Sakakibara, Shuhei
	Ogawa, Seishi
	Kumanogoh, Atsushi
	Okada, Yukinori
citation_publisher	Nature Research
citation_language	英語
citation_date	2025-07-28
citation_journal_title	Nature Genetics
citation_volume	57
citation_issue	8
citation_firstpage	1905
citation_lastpage	1921
citation_doi	https://doi.org/10.1038/s41588-025-02266-3
citation_public_url	https://hdl.handle.net/11094/102930

Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution

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