AUTHOR=Li Shun , Wu Bin , Ling Yun , Guo Mingquan , Qin Boyin , Ren Xiaonan , Wang Chao , Yang Hua , Chen Lixiang , Liao Yixin , Liu Yang , Peng Xiuhua , Xu Chunhua , Wang Zhenyan , Shen Yinzhong , Chen Jun , Liu Li , Niu Bowen , Zhu Mengmin , Liu Lingling , Li Feng , Zhu Tongyu , Zhu Zhaoqin , Zhou Xiaohui , Lu Hongzhou 

TITLE=Epigenetic Landscapes of Single-Cell Chromatin Accessibility and Transcriptomic Immune Profiles of T Cells in COVID-19 Patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.625881

DOI=10.3389/fimmu.2021.625881

ISSN=1664-3224

ABSTRACT=T cells play a critical role in coronavirus diseases. How they do so in COVID-19 may be revealed by analyzing epigenetic chromatin accessibility of cis- and trans-regulatory elements and creating transcriptomic immune profiles. We performed single-cell Assay for Transposase Accessible Chromatin (scATAC) and RNA (scRNA) sequencing on peripheral blood mononuclear cells (PBMCs) from COVID-19 severely ill/critical patients (SCPs), moderate patients (MPs) and healthy volunteer controls (HCs). 76,570 and 107,862 single cells were used respectively for analyzing the characteristics of chromatin accessibility and transcriptomic immune profiles by application of scATAC-seq (9 cases) and scRNA-seq (15 cases). scATAC-seq detected 28,535 different peaks in the three groups, among these peaks 41.6% and 10.7% were located in the promoter and enhancer regions respectively. Compared with HCs, the peak-located genes in total T, subsets CD4+ T and CD8+ T cells from SCPs and MPs were enriched in inflammatory pathways, e.g. MAPK signaling pathway, TNF signaling pathway etc. The motifs of TBX21 were less accessible in the CD4+ T cells of SCPs compared with those in MPs. Furthermore, scRNA-seq showed that the proportion of T cells, especially CD4+ T cells, was decreased in SCPs and MPs compared with HCs. Transcriptomic results revealed histone-related genes, and inflammatory genes such as NFKBIA, S100A9, PIK3R1 were highly expressed in the total T, CD4+ T and CD8+ T cells, both in SCPs and MPs cases. In the CD4+ T cells, decreased T helper-1 (Th1) cells were observed in SCPs and MPs. In the CD8+ T cells, activation markers such as CD69 and HLA class II genes (HLA-DRA, HLA-DRB1 and HLA-DRB5) were up-regulated in SCPs. An integrated analysis of the scATAC-seq and scRNA-seq data showed some consistency between the approaches. Cumulatively, we have generated a landscape of chromatin epigenetic status and transcriptomic immune profiles of T cells in COVID-19 patients. This has provided a deeper dissection of the characteristics of the T cells involved at a higher resolution than previously obtained merely by scRNA-seq analysis. Our data suggest that T cell inflammatory states accompanied by defective functions in CD4+ T cellsin SCPs maybe key factors determining pathogenesis and recovery in COVID-19.