Two reactive behaviors of chondrocytes in an IL-1β-induced inflammatory environment revealed by the single-cell RNA sequencing.
Two reactive behaviors of chondrocytes in an IL-1β-induced inflammatory environment revealed by the single-cell RNA sequencing.
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单细胞 RNA 测序揭示了 IL-1β 诱导的炎症环境中软骨细胞的两种反应行为
DOI：
10.18632/aging.202857
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发表时间：
2021-04-20
期刊：
影响因子：
--
通讯作者：
Xiao J
中科院分区：
文献类型：
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作者：
Gao C;Pu H;Zhou Q;Tao T;Liu H;Sun X;He X;Xiao J
目的：研究在白细胞介素（IL）-1β诱导的炎症环境中培养的体外扩增软骨细胞的异质反应。方法：将人关节软骨细胞在体外扩增 13 天，并用 IL-1β 处理 0、24 和 48 小时。收集细胞并进行单细胞RNA测序。使用多种生物信息学工具来确定定义软骨细胞生理学的特征。结果：在初始阶段鉴定出具有不同表达模式的两个主要细胞簇，并且具有与炎症进展相符的异质性变异。它们转化为两个末端细胞簇，其中一个细胞簇分别通过“炎症反应”和“非典型炎症反应”两条途径表现出 OA 表型和促炎症特征。所涉及的细胞簇与 OA 患者的天然软骨内的细胞类型表现出内在的关系。控制细胞向 OA 表型转化的基因与通过 NFKB 的肿瘤坏死因子 (TNF) 信号通路、上调的 KRAS 信号通路、IL2/STAT5 信号通路以及与细胞凋亡和活性氧相关的通路有关。结论：IL-1β诱导的炎症进展下体外扩增的软骨细胞表现出异质性。最初的细胞簇之一可以通过所谓的炎症反应路径转化为促炎症亚群，这可能作为缓解 OA 进展的核心目标。
Objective: To investigate the heterogeneous responses of in vitro expanded chondrocytes, which were cultured in an interleukin (IL)-1β -induced inflammatory environment. Method: Human articular chondrocytes were expanded, in vitro, for 13 days and treated with IL-1β for 0, 24, and 48 h. Cells were collected and subjected to single-cell RNA sequencing. Multiple bioinformatics tools were used to determine the signatures that define chondrocyte physiology. Results: Two major cell clusters with distinct expression patterns were identified at the initial phase and were with heterogeneous variation that coincides with inflammation progress. They transformed into two terminal cell clusters one of which exhibited OA-phenotype and proinflammatory characteristics through two paths, “response-to-inflammation” and “atypical response-to-inflammation”, respectively. The involved cell clusters exhibited intrinsic relationship with cell types within native cartilage from OA patients. Genes controlling cell transformation to OA-phenotype were relating to the tumor necrosis factor (TNF) signaling pathway via NFKB, up-regulated KRAS signaling and the IL2/STAT5 signaling pathway and pathways relating to apoptosis and reactive oxygen species. Conclusion: The in vitro expanded chondrocytes under IL-1β-induced inflammatory progression behave heterogeneously. One of the initial cell clusters could transform into a proinflammatory subpopulation through a termed response-to-inflammation path, which may serve as the core target to alleviate OA progression.