Single cell multi-omic analysis identifies key genes differentially expressed in innate lymphoid cells from COVID-19 patients

单细胞多组学分析确定了 COVID-19 患者先天淋巴细胞中差异表达的关键基因

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作者:Abhinav Kaushik, Iris Chang, Xiaorui Han, Ziyuan He, Zsolt I Komlosi, Xuhuai Ji, Shu Cao, Cezmi A Akdis, Scott Boyd, Bali Pulendran, Holden T Maecker, Mark M Davis, R Sharon Chinthrajah, Rosemarie H DeKruyff #, Kari C Nadeau #

Discussion

Overall, this study provides mechanistic insights into the characteristics of ILC subsets activated during COVID-19 infection.

Methods

To gain insight into the role of ILCs in the pathology and recovery from COVID-19 infection, we employed a multi-omics approach consisting of Abseq and targeted mRNA sequencing to respectively probe the surface marker expression, transcriptional profile and heterogeneity of ILCs in peripheral blood of patients with COVID-19 compared with healthy controls.

Results

We found that the frequency of ILC1 and ILC2 cells was significantly increased in COVID-19 patients. Moreover, all ILC subsets displayed a significantly higher frequency of CD69-expressing cells, indicating a heightened state of activation. ILC2s from COVID-19 patients had the highest number of significantly differentially expressed (DE) genes. The most notable genes DE in COVID-19 vs healthy participants included a) genes associated with responses to virus infections and b) genes that support ILC self-proliferation, activation and homeostasis. In addition, differential gene regulatory network analysis revealed ILC-specific regulons and their interactions driving the differential gene expression in each ILC.

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