日本大阪大学Yukinori Okada团队的最新研究探明了从单细胞分辨率的多层组学数据中破译状态依赖性免疫特征。相关论文于2025年7月28日发表在《自然—遗传学》杂志上。

该课题组构建了一个免疫细胞图谱，包括来自235名日本人的150万个外周血单个核细胞的单细胞转录组学、宿主遗传学、血浆蛋白质组学和肠道宏基因组学，包括2019年冠状病毒病（COVID-19）患者和健康个体。研究组绘制了生殖系遗传对免疫细胞类型和细胞状态内基因表达的影响。研究人员阐明了细胞类型和环境特异性人类白细胞抗原（HLA）以及与T细胞和B细胞受体库的全基因组关联。共定位主题动态遗传调控提供了更好的全基因组关联信号的理解。差异基因和蛋白质表达分析描述了多基因风险的细胞类型和环境特异性影响。包括马赛克染色体改变、Y染色体丢失和线粒体DNA （mtDNA）异质性在内的各种体细胞突变被投射到单细胞分辨率。该研究团队确定了体细胞突变细胞特有的免疫特征。总的来说，免疫细胞以细胞状态依赖的方式动态调节，具有多组学特征。

据介绍，目前的分子定量性状定位目录大多是批量分辨率的，并且以欧洲人为中心。

附：英文原文

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

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, 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

Issue&Volume: 2025-07-28

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.

DOI: 10.1038/s41588-025-02266-3

Source: https://www.nature.com/articles/s41588-025-02266-3