Altered Monocyte Subsets in Kawasaki Disease Revealed by Single-cell RNA-Sequencing.
Altered Monocyte Subsets in Kawasaki Disease Revealed by Single-cell RNA-Sequencing.
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DOI：
10.2147/jir.s293993
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发表时间：
2021
影响因子：
4.5
通讯作者：
Gong F
中科院分区：
文献类型：
--
作者：
Geng Z;Tao Y;Zheng F;Wu L;Wang Y;Wang Y;Sun Y;Fu S;Wang W;Xie C;Zhang Y;Gong F
川崎病是一种以免疫反应紊乱为特征的疾病，其病因尚不清楚。单核细胞是机体先天免疫系统的重要成员；然而，由于其不明确的异质性和复杂的功能，其在KD中的作用仍然难以捉摸。我们的目的是全面描述健康和KD婴儿的单核细胞异质性，并揭示KD的潜在机制。外周血单核细胞富集于两名健康婴儿和两名KD婴儿的外周血样本。scRNA-seq获得单核细胞的转录组图谱。利用生物信息分析鉴定单核细胞亚群，探索其功能和分化状态。流式细胞术验证SELL+CD14+CD16-单核细胞。在健康婴儿中鉴定出三种单核细胞亚群，包括CD14+CD16-单核细胞、CD14+CD16+单核细胞和CD14LowCD16+单核细胞。细胞轨迹分析表明，这三个单核细胞亚群呈线性分化，具有不同的生物学功能。此外，发现与中性粒细胞活化有关的低分化的SELL+CD14+CD16-单核细胞在KD中扩增。我们的研究结果为解读健康婴儿的单核细胞异质性提供了宝贵的资源，揭示了KD患者单核细胞亚群的改变，为KD的诊断和治疗提供了潜在的生物标志物。
Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of the body’s innate immune system; however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. We aim to comprehensively delineate monocyte heterogeneity in healthy and KD infants and to reveal the underlying mechanism for KD. Peripheral monocytes were enriched from peripheral blood samples of two healthy infants and two KD infants. scRNA-seq was performed to acquire the transcriptomic atlas of monocytes. Bio-information analysis was utilized to identify monocyte subsets and explore their functions and differentiation states. SELL+CD14+CD16- monocytes were validated using flow cytometry. Three monocyte subsets were identified in healthy infants, including CD14+CD16- monocytes, CD14+CD16+ monocytes, and CD14LowCD16+ monocytes. Cell trajectory analysis revealed that the three monocyte subsets represent a linear differentiation, and possess different biological functions. Furthermore, SELL+CD14+CD16- monocytes, which were poorly differentiated and relating to neutrophil activation, were found to be expanded in KD. Our findings provide a valuable resource for deciphering the monocyte heterogeneity in healthy infants and uncover the altered monocyte subsets in KD patients, suggesting potential biomarkers for KD diagnosis and treatment.