Gao Yuehan, Li He, Li Zhaohuai, Xie Lihui, Liu Xiuxing, Huang Zhaohao, Chen Binyao, Lin Xianchai, Wang Xianggui, Zheng Yingfeng, Su Wenru
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
Eye Center of Xiangya Hospital, Central South University, Changsha, China; and
J Immunol. 2021 Aug 1;207(3):837-848. doi: 10.4049/jimmunol.2100094. Epub 2021 Jul 19.
Dendritic cells (DCs) are critical for pathogen recognition and Ag processing/presentation. Human monocyte-derived DCs (moDCs) have been extensively used in experimental studies and DC-based immunotherapy approaches. However, the extent of human moDC and peripheral DCs heterogeneity and their interrelationship remain elusive. In this study, we performed single-cell RNA sequencing of human moDCs and blood DCs. We identified seven subtypes within moDCs: five corresponded to type 2 conventional DCs (cDC2s), and the other two were CLEC10ACD127 cells with no resemblance to any peripheral DC subpopulations characterized to date. Moreover, we defined five similar subtypes in human cDC2s, revealed the potential differentiation trajectory among them, and unveiled the transcriptomic differences between moDCs and cDC2s. We further studied the transcriptomic changes of each moDC subtype during maturation, demonstrating and as maturation markers and and as markers for immature DCs. These findings will enable more accurate functional/developmental analyses of human cDC2s and moDCs.
树突状细胞（DCs）对于病原体识别和抗原加工/呈递至关重要。人单核细胞衍生的DCs（moDCs）已广泛应用于实验研究和基于DC的免疫治疗方法。然而，人moDCs和外周DCs的异质性程度及其相互关系仍不清楚。在本研究中，我们对人moDCs和血液DCs进行了单细胞RNA测序。我们在moDCs中鉴定出七个亚型：五个对应于2型传统DCs（cDC2s），另外两个是CLEC10A+CD127细胞，与迄今为止所描述的任何外周DC亚群均不相似。此外，我们在人cDC2s中定义了五个相似的亚型，揭示了它们之间潜在的分化轨迹，并揭示了moDCs和cDC2s之间的转录组差异。我们进一步研究了每个moDC亚型在成熟过程中的转录组变化，证明了[具体基因1]和[具体基因2]作为成熟标志物，以及[具体基因3]和[具体基因4]作为未成熟DCs的标志物。这些发现将有助于对人cDC2s和moDCs进行更准确的功能/发育分析。
