Single-Cell Transcriptome Profiling Reveals Neutrophil Heterogeneity and Functional Multiplicity in the Early Stage of Severe Burn Patients.

Jiamin Huang,Binwei Sun,Linbin Li,Yiming Shao,Yunxi Yang,Ran Sun,Zhechen Zhu,Dongdong Ji,Lu Liu,Yi Chen

doi:10.3389/fimmu.2021.792122

Jiamin Huang, Binwei Sun + Show 8 more

Open Access

https://doi.org/10.3389/fimmu.2021.792122

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Abstract

The pathophysiological mechanisms, especially the roles of immune cells, underlying early stages of severe burn injury have not yet been fully clarified. Here, we analyzed circulating neutrophils (PMNs) in healthy donors and early burned patients by single-cell RNA sequencing to provide a comprehensive transcriptional landscape of PMNs in heterogeneity and functional multiplicity. Circulating PMNs in the healthy donors and burned groups were divided into five subgroups (G3, G4, G5a, G5b, G5c) with different functions. The dominant subsets of PMNs in homeostasis and burn injury significantly differed between groups. In addition, cells in the same subpopulation had the same core identity markers but performed different functions in healthy and burned states. Under burned conditions, PMN activation was very evident and accompanied by clear degranulation and metabolic abnormalities. Interestingly, was found that PMN activation, degranulation, chemotaxis, phagocytosis and reactive oxygen species (ROS) production in burned patients significantly differed between day 1 and days 2 or 3, thus providing a theoretical basis for PMN interventions in early burn stages. Significantly, previously undescribed transcription factors were also identified, including ZNF-787, ZNF-467, ZNF-189, ZNF-770, ZNF-262. In conclusion, this study conducted for the first time a detailed analysis of the heterogeneity and functional multiplicity of PMNs in early stages of severe burn injuries. Our findings attempted to clarify the influence of PMN heterogeneity on the pathophysiology and related mechanisms of burn injuries, which can provide new ideas for further research in burn intervention.

Highlights

Burn injury is a common form of trauma [1]
We reviewed the electronic medical records of patients with extensive burn injuries between
We linked the neutrophil population defined by our scRNA-seq to the data reported by Xie et al [18] (Figure 1F)

Summary

Introduction

Burn injury is a common form of trauma [1]. Burn wound prognosis depends on the severity of the burn injuries. Patients with extensive burn injuries are often in shock when they are admitted to the hospital, because of impaired skin protection, which induces systemic changes. Neutrophil Heterogeneity in Burn Injury such as tissue fluid outflow, blood volume reduction and tissue damage. Active fluid rehydration is a common clinical method used to address shock, which can restore blood perfusion and decrease ischemic damage to cells, tissues and organs [4]. Treatment is key to improving prognosis and can decrease systemic inflammatory response syndrome, sepsis, multiple organ failure and other life-threatening conditions in patients [7]. Simple fluid rehydration can relieve the shock state of the body, it does not appear to fundamentally alleviate the disorder within the internal environment of the body, the immune microenvironment [8], which creates favorable conditions for uncontrolled infection

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Conclusion