A single-cell transcriptomic atlas of immune cells in Wilson disease identifies copper-specific immune regulation
Shuya Wang,
Xianlei Sun,
Qingxuan Xin,
Jianxiang Shi,
Jin Li,
Huilin Zhang,
Mengjiao Xue,
Fanxiang Yin,
Zan Qiu,
Xiaoqian Wang,
Nannan Sun,
Yingmei Li,
Yaoyao Chen,
Liyan Fu,
Chaoqi Li,
Shaohua Yan,
Xian Zhao,
Bolin Jue,
Yanxia Gao,
Baohong Yue,
Bo Qin,
Yong Jiang,
Rongqun Guo
Affiliations
Shuya Wang
Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Xianlei Sun
Basic Medical Research Center, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China
Qingxuan Xin
Department of Laboratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
Jianxiang Shi
Precision Medicine Center, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
Jin Li
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Huilin Zhang
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Mengjiao Xue
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Fanxiang Yin
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Zan Qiu
Precision Medicine Center, Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
Xiaoqian Wang
Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Nannan Sun
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Yingmei Li
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Yaoyao Chen
Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Liyan Fu
Department of Laboratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China
Chaoqi Li
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Shaohua Yan
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Xian Zhao
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Bolin Jue
Xinxiang Medical University College of Basic Medical Sciences, Xinxiang, Henan, China
Yanxia Gao
Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Baohong Yue
Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Corresponding author
Bo Qin
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Corresponding author
Yong Jiang
State Key Laboratory of Antiviral Drugs, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Henan Key Laboratory of Critical Care Medicine, Department of Emergency Medicine, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, China; Institute of Infection and Immunity, Henan Academy of Innovations in Medical Science, Zhengzhou, Henan, China; Corresponding author
Rongqun Guo
Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Corresponding author
Summary: Wilson disease (WD) is caused by mutations of the copper-transporting gene, ATP7B, leading to abnormal copper metabolism. A better characterization of WD is essential in understanding the effects of excess copper and how it disrupts immune regulation and hematopoietic development. Furthermore, the exploration of the relationship between copper-mediated proliferation or cuproptosis and immune regulation is critical for developing new immune therapies. Therefore, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) to develop an atlas of the immune landscape. Cells were clustered into several immune subsets, and cuproptosis-associated genes were assessed. Differential expression analysis was performed to identify WD-specific signatures by comparing transcriptome profiles of patients with WD with HDs. Excess copper impaired immune homeostasis and hematopoietic development. Then, we developed a map of the immune landscape of patients with WD. Excess copper is involved in the metabolic reprogramming of immune cells, such as glycolysis in CD14+ monocytes. We found that the antigen processing-related pathway is dysregulated in immune cells of patients with WD. Our study revealed that abnormal copper concentration influences the expression of HLA-I and HLA-II molecules. It is noteworthy that a high concentration of intracellular copper differs significantly from the high concentration of extracellular copper. We have also identified a gene set of neurologic abnormalities, which were dysregulated in PBMCs of patients with WD. We also observed abnormal expression of cuproptosis-associated genes in proliferating or malignant cells, providing new insights into the application of cuproptosis in cancer treatment.
