Single-Cell Transcriptome Profiling Reveals Neutrophil Heterogeneity and Functional Multiplicity in the Early Stage of Severe Burn Patients.
Single-Cell Transcriptome Profiling Reveals Neutrophil Heterogeneity and Functional Multiplicity in the Early Stage of Severe Burn Patients.
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单细胞转录组分析揭示了严重烧伤患者早期的中性粒细胞异质性和功能多样性。
DOI：
10.3389/fimmu.2021.792122
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发表时间：
2021
影响因子：
7.3
通讯作者：
Sun B
中科院分区：
文献类型：
--
作者：
Huang J;Zhu Z;Ji D;Sun R;Yang Y;Liu L;Shao Y;Chen Y;Li L;Sun B
严重烧伤早期的病理生理机制，特别是免疫细胞的作用尚未完全阐明。在这里，我们通过单细胞RNA测序分析了健康供体和早期烧伤患者的循环中性粒细胞（pmn），以提供pmn异质性和功能多样性的全面转录景观。将健康供者和烧伤组循环pmn分为G3、G4、G5a、G5b、G5c 5个功能不同的亚组。在体内平衡和烧伤损伤中，pmn的优势亚群在两组间存在显著差异。此外，同一亚群中的细胞具有相同的核心身份标记，但在健康和燃烧状态下执行不同的功能。在烧伤条件下，PMN激活非常明显，并伴有明显的脱颗粒和代谢异常。有趣的是，我们发现烧伤患者的PMN激活、脱颗粒、趋化、吞噬和活性氧（ROS）产生在第1天与第2天或第3天之间存在显著差异，从而为烧伤早期PMN干预提供了理论依据。值得注意的是，之前未描述的转录因子也被鉴定出来，包括ZNF-787， ZNF-467, ZNF-189, ZNF-770, ZNF-262。总之，本研究首次对严重烧伤早期pmn的异质性和功能多样性进行了详细分析。本研究旨在阐明PMN异质性对烧伤病理生理及相关机制的影响，为进一步开展烧伤干预研究提供新的思路。
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.
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影响因子：
64.8
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