Qing Gao, Zhiyuan Wu, Jinge Yu, Yuqing Miao, Zuoguan Chen, Yongpeng Diao, Jinfeng Yin, Junnan Jia, Yijia Guo, Weimin Li, Yongjun Li
Graduate School of Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.
Department of Vascular Surgery, National Centre of Gerontology, Beijing Hospital, Beijing, China.
Front Cell Dev Biol. 2021 Oct 4;9:761300. doi: 10.3389/fcell.2021.761300. eCollection 2021.
Takayasu Arteritis (TA) is a highly specific vascular inflammation and poses threat to patients' health. Although some patients have accepted medical treatment, their culprit lesions require surgical management (TARSM). This study aimed at dissecting the transcriptomes of peripheral blood mononuclear cells (PBMCs) in these patients and to explore potential clinical markers for TA development and progression. Peripheral blood were collected from four TA patients requiring surgical management and four age-sex matched healthy donors. Single cell RNA sequencing (scRNA-seq) was adopted to explore the transcriptomic diversity and function of their PBMCs. ELISA, qPCR, and FACS were conducted to validate the results of the analysis. A total of 29918 qualified cells were included for downstream analysis. Nine major cell types were confirmed, including CD14 monocytes, CD8 T cells, NK cells, CD4 T cells, B cells, CD16 monocytes, megakaryocytes, dendritic cells and plasmacytoid dendritic cells. CD14 monocytes (50.0 vs. 39.3%, < 0.05) increased in TA patients, as validated by FACS results. TXNIP, AREG, THBS1, and CD163 increased in TA patients. ILs like IL-6, IL-6STP1, IL-6ST, IL-15, and IL-15RA increased in TA group. Transcriptome heterogeneities of PBMCs in TA patients requiring surgical management were revealed in the present study. In the patients with TA, CD14 monocytes and gene expressions involved in oxidative stress were increased, indicating a new treatment and research direction in this field.
大动脉炎(TA)是一种高度特异性的血管炎症,对患者的健康构成威胁。尽管一些患者已接受药物治疗,但其主要病变仍需手术处理(TARSM)。本研究旨在剖析这些患者外周血单个核细胞(PBMC)的转录组,并探索TA发生和发展的潜在临床标志物。从4例需要手术处理的TA患者和4例年龄、性别匹配的健康供体中采集外周血。采用单细胞RNA测序(scRNA-seq)来探索其PBMC的转录组多样性和功能。进行酶联免疫吸附测定(ELISA)、定量聚合酶链反应(qPCR)和荧光激活细胞分选(FACS)以验证分析结果。共有29918个合格细胞纳入下游分析。确认了9种主要细胞类型,包括CD14单核细胞、CD8 T细胞、自然杀伤(NK)细胞、CD4 T细胞、B细胞、CD16单核细胞、巨核细胞、树突状细胞和浆细胞样树突状细胞。FACS结果证实,TA患者中CD14单核细胞增加(50.0%对39.3%,P<0.05)。TA患者中硫氧还蛋白相互作用蛋白(TXNIP)、双调蛋白(AREG)、血小板反应蛋白1(THBS1)和CD163增加。TA组中白细胞介素(IL)如IL-6、IL-6信号转导蛋白1(IL-6STP1)、IL-6信号转导蛋白(IL-6ST)、IL-15和IL-15受体α(IL-15RA)增加。本研究揭示了需要手术处理的TA患者PBMC的转录组异质性。在TA患者中,CD14单核细胞和参与氧化应激的基因表达增加,为该领域提供了新的治疗和研究方向。