Single-cell transcriptomic characterization reveals the landscape of airway remodeling and inflammation in a cynomolgus monkey model of asthma.
Single-cell transcriptomic characterization reveals the landscape of airway remodeling and inflammation in a cynomolgus monkey model of asthma.
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单细胞转录组学特征分析揭示了食蟹猴哮喘模型中气道重塑与炎症的全貌。
DOI：
10.3389/fimmu.2022.1040442
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发表时间：
2022
影响因子：
7.3
通讯作者：
Xie, Yicheng
中科院分区：
文献类型：
--
作者：
Wang, Yingshuo;Dong, Xinyan;Pan, Caizhe;Zhu, Cihang;Qi, Hantao;Wang, Yifan;Wei, Hao;Xie, Qiangmin;Wu, Lei;Shen, Huijuan;Li, Shuxian;Xie, Yicheng
猴子疾病模型在遗传、解剖和生理特征方面与人类相似，对于理解疾病机制和评估生物治疗的效率具有重要意义。在这里，我们在食蟹猴中建立了 A.suum 诱导的哮喘模型，通过单细胞 RNA 测序 (scRNA-seq) 来分析肺部气道炎症和重塑。哮喘模型导致气道高反应性和重塑，由肺功能测试和组织学特征证明。 scRNA-seq 揭示该模型提高了基质细胞、上皮细胞和间充质细胞 (MC) 的数量。特别是，该模型增加了肺部内皮细胞（EC）、成纤维细胞（Fib）和平滑肌细胞（SMC）的数量，上调了与EC和Fib中细胞迁移和血管生成丰富的细胞功能相关的基因表达，以及SMC中VEGF驱动的细胞增殖、凋亡过程和补体激活。有趣的是，我们发现了一种新的 Fib 亚型，可以介导哮喘肺部的 I 型炎症。此外，哮喘肺部的 MC 被发现可以调节气道重塑和免疫反应，基因表达升高，丰富细胞迁移、增殖、血管生成和先天免疫反应。采集肺组织时，哮喘肺内上皮细胞的数量不仅发生变化，而且其基因表达也发生显着改变，IL-17信号通路的生物学过程丰富，大多数上皮细胞亚型发生凋亡。此外，泛素过程和 DNA 修复在纤毛上皮细胞中更为普遍。最后，细胞间相互作用分析揭示了基质细胞、MC 和巨噬细胞之间的复杂网络，有助于哮喘和气道重塑的发展。我们的研究结果为理解哮喘猴模型气道重塑和炎症的原理提供了重要的资源，也为未来哮喘的治疗，特别是以气道重塑为特征的难治性哮喘提供了宝贵的提示。
Monkey disease models, which are comparable to humans in terms of genetic, anatomical, and physiological characteristics, are important for understanding disease mechanisms and evaluating the efficiency of biological treatments. Here, we established an A.suum-induced model of asthma in cynomolgus monkeys to profile airway inflammation and remodeling in the lungs by single-cell RNA sequencing (scRNA-seq). The asthma model results in airway hyperresponsiveness and remodeling, demonstrated by pulmonary function test and histological characterization. scRNA-seq reveals that the model elevates the numbers of stromal, epithelial and mesenchymal cells (MCs). Particularly, the model increases the numbers of endothelial cells (ECs), fibroblasts (Fibs) and smooth muscle cells (SMCs) in the lungs, with upregulated gene expression associated with cell functions enriched in cell migration and angiogenesis in ECs and Fibs, and VEGF-driven cell proliferation, apoptotic process and complement activation in SMCs. Interestingly, we discover a novel Fib subtype that mediates type I inflammation in the asthmatic lungs. Moreover, MCs in the asthmatic lungs are found to regulate airway remodeling and immunological responses, with elevated gene expression enriched in cell migration, proliferation, angiogenesis and innate immunological responses. Not only the numbers of epithelial cells in the asthmatic lungs change at the time of lung tissue collection, but also their gene expressions are significantly altered, with an enrichment in the biological processes of IL-17 signaling pathway and apoptosis in the majority of subtypes of epithelial cells. Moreover, the ubiquitin process and DNA repair are more prevalent in ciliated epithelial cells. Last, cell-to-cell interaction analysis reveals a complex network among stromal cells, MCs and macrophages that contribute to the development of asthma and airway remodeling. Our findings provide a critical resource for understanding the principle underlying airway remodeling and inflammation in a monkey model of asthma, as well as valuable hints for the future treatment of asthma, especially the airway remodeling-characterized refractory asthma.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
缺氧 hUCMSC 来源的细胞外囊泡减轻慢性哮喘小鼠的过敏性气道炎症和气道重塑
影响因子：
7.5
作者：
Dong L;Wang Y;Zheng T;Pu Y;Ma Y;Qi X;Zhang W;Xue F;Shan Z;Liu J;Wang X;Mao C
通讯作者：
Mao C
影响因子：
76.2
作者：
Chupp, Geoffrey L.;Bradford, Eric S.;ten Brinke, Anneke
通讯作者：
ten Brinke, Anneke
影响因子：
14.8
作者：
Efremova, Mirjana;Vento-Tormo, Miquel;Vento-Tormo, Roser
通讯作者：
Vento-Tormo, Roser