Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

Lulin Huang; Yi Shi; Bo Gong; Li Jiang; Xiaoqi Liu; Jialiang Yang; Juan Tang; Chunfang You; Qi Jiang; Bo Long; Tao Zeng; Mei Luo; Fanwei Zeng; Fanxin Zeng; Shuqiang Wang; Xingxiang Yang; Zhenglin Yang

The peripheral blood mononuclear cells (PBMCs) of each individual were isolated from the whole blood, and the single-cell mRNA sequencing (ScRNA-Seq) analysis of the PBMCs was performed on the 10 X genomics platform with Chromium Next GEM Single Cell V(D)J Reagent Kits v1.1 (Fig. 1A ). After quality control, we obtained 134,620 PBMC cells, 83,387 TCR clones, and 12,601 BCR clones from the 16 samples. In these samples, we identified 17 completely different PBMC cell types, which could be further divided into 56 cell subtypes according to marker genes of the 134,620 cells (Fig. 1B, 1C, 1D and Table S2 ). The 17 cell types included CD4+ T cells identified by LTB and IL7R markers, CD8+ T cells identified by LEF1 and CD8A, CD1C+_B dendritic cells identified by BSET1 and CD1D, CD4+ cytotoxic T cells identified by CST7 and CCL4, CD8 cytotoxic T cells identified by CD3D and CD8A, and other cell types (Fig. 1C, Table S2 ). This suggests that human PBMCs have evolved highly differentiated cell subtypes to resist the invasion of pathogens (18) . There were three main states in the analysis process for reconstructing the developmental trajectories of the 56 cell subtypes, which showed a continuous trajectory of differentiating PBMCs (Fig. 1E, Fig. S2 ). In addition, 23 totally new candidate marker genes linked to 22 cell subtypes were identified (Fig. S3) , suggesting potential roles for these newly discovered cell markers in the identification and functional study of these subtypes.