Single-cell transcriptome profiling reveals heterogeneous neutrophils with prognostic values in sepsis
Yucai Hong,
Lin Chen,
Jian Sun,
Lifeng Xing,
Yi Yang,
Xiaohong Jin,
Huabo Cai,
Lianlian Dong,
Liping Zhou,
Zhongheng Zhang
Affiliations
Yucai Hong
Department of Emergency Medicine, Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Lin Chen
Department of Critical Care Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China
Jian Sun
Department of Critical Care Medicine, Lishui Center Hospital, Lishui, Zhejiang 323000, China
Lifeng Xing
Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Yi Yang
Department of Emergency Medicine, The Second Hospital of Jiaxing, Jiaxing, 314000, P.R.China
Xiaohong Jin
Department of Emergency Medicine, The Affiliated Wenling Hospital of Wenzhou Medical University, Wenling 317500, Zhejiang Province, China
Huabo Cai
Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Lianlian Dong
Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Liping Zhou
Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Zhongheng Zhang
Department of Emergency Medicine, Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China; Key Laboratory of Digital Technology in Medical Diagnostics Of Zhejiang Province, Hangzhou, Zhejiang, China; Corresponding author
Summary: Neutrophils constitute the largest proportion of nucleated peripheral blood cells, and neutrophils have substantial heterogeneity. We profiled nearly 300,000 human peripheral blood cells in this study using single-cell RNA sequencing. A large proportion (>50%) of these cells were annotated as neutrophils. Neutrophils were further clustered into four subtypes, including Neu1, Neu2, Neu3, and Neu4. Neu1 is characterized by high expression of MMP9, HP, and RGL4. Neu1 was associated with septic shock and significantly correlated with the sequential organ failure assessment (SOFA) score. A gene expression module in Neu1 named Neu1_C (characterized by expression of NFKBIA, CXCL8, G0S2, and FTH1) was highly predictive of septic shock with an area under the curve of 0.81. The results were extensively validated in external bulk datasets by using single-cell deconvolution methods. In summary, our study establishes a general framework for studying neutrophil-related mechanisms, prognostic biomarkers, and potential therapeutic targets for septic shock.
