Single-Cell Genomics Elucidates Molecular Variations and Regulatory Mechanisms in Circulating Immune Cells

作者：Jianhua Yin, Yuhui Zheng, Zhuoli Huang, Wenwen Zhou, Yue Yuan, Pengfei Cai, Yong Bai, Shichen Yang, Yue Gao, Shanshan Duan, Yang Wang, Wenxi Zhang, Xinyu Zhang, Yilin Wei, Zekai Xu, Yaling Huang, Ying Liu, Weikai Wang, Tao Yang, Jingzhi Lv, Zhongjin Zhang, Xiaoya Chen, Xiru Zhang, Fupeng Li, Yan Zhang, Guodan Zeng, Xue Wang, Wen‐Juan Ma, Guixue Hou, Shijie Hao, Chang Liu, Chang Liu, Yiwei Lai, Bo Wang, Yuxiang Li, Wenwei Zhang, Peng Gao, Jun Xie, Miguel A. Esteban, Ying Gu, Jiansong Ji, Ting Qi, Boxiang Liu, Jian Wang, Jian Yang, Xun Xu, Longqi Liu, Xin Jin, Chuanyu Liu, Chuanyu Liu · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.01.26.634963 · 被引用次数：3 · 研究领域：T-cell and B-cell Immunology、Immune cells in cancer、Immune Cell Function and Interaction

Abstract The human peripheral blood displays diverse molecular characteristics across populations, understanding the drivers and underlying mechanisms of which remains challenging. Here, we introduce the Chinese Immune Multi-Omics Atlas (CIMA), elucidating sex-, age-, and genetic-related molecular variations by analyzing multi-omics data from 428 adults with over 10 million immune cells. CIMA generated an enhancer-driven gene regulatory network, identifying 237 high-quality regulons and revealing cell type-specific regulatory mechanisms. Additionally, 11,521 lead cis -expression quantitative trait loci (eQTLs) and 46,339 chromatin accessibility QTLs (caQTLs) were identified at cell type level. CIMA also uncovered pleiotropic associations among immune-related disease risk loci, eQTLs, and caQTLs in a cell type-specific manner. Lastly, a novel cell language model, CIMA-CLM, was developed to predict chromatin accessibility and noncoding variant effects using chromatin sequences and gene expressions. This work represents a population-scale multi-omics resource of human immune cells, providing a valuable reference for future investigation of immune-related diseases.