Single-Cell Sequencing Reveals MYOF-Enriched Monocyte/Macrophage Subcluster as a Favorable Prognostic Factor in Sepsis

作者全名："Zhang, Yi-Fan; Yi, Zhu-Jun; Zhang, Wen-Feng; Yang, Lian; Qi, Feng; Yu, Ting; Zhu, Zhu; Li, Ming-Jie; Cheng, Yao; Zhao, Lei; Gong, Jian-Ping; Li, Pei-Zhi"

作者地址："[Zhang, Yi-Fan; Zhang, Wen-Feng; Yang, Lian; Qi, Feng; Yu, Ting; Zhu, Zhu; Li, Ming-Jie; Cheng, Yao; Zhao, Lei; Gong, Jian-Ping; Li, Pei-Zhi] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China; [Yi, Zhu-Jun] Chongqing Univ Three Gorges Hosp, Dept Hepatobiliary Surg, Chongqing 404100, Peoples R China"

通信作者："Li, PZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China."

来源：ADVANCED BIOLOGY

ESI学科分类：　

WOS号：WOS:001180592600001

JCR分区：Q3

影响因子：3.2

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：monocytes and macrophages; MYOF; peripheral blood mononuclear cells (PBMCs); prognostic marker; sepsis; single-cell analysis

摘要："This research utilized single-cell RNA sequencing to map the immune cell landscape in sepsis, revealing 28 distinct cell clusters and categorizing them into nine major types. Delving into the monocyte/macrophage subclusters, 12 unique subclusters are identified and pathway enrichment analyses are conducted using KEGG and GO, discovering enriched pathways such as oxidative phosphorylation and antigen processing. Further GSVA and AUCell assessments show varied activation of interferon pathways, especially in subclusters 4 and 11. The clinical correlation analysis reveals genes significantly linked to survival outcomes. Additionally, cellular differentiation in these subclusters is explored. Building on these insights, the differential gene expression within these subclusters is specifically scrutinized, which reveal MYOF as a key gene with elevated expression levels in the survivor group. This finding is further supported by in-depth pathway enrichment analysis and the examination of cellular differentiation trajectories, where MYOF's role became evident in the context of immune response regulation and sepsis progression. Validating the role of the MYOF gene in sepsis, a dose-dependent response to LPS in THP-1 cells and C57 mice is observed. Finally, inter-cellular communications are analyzed, particularly focusing on the MYOF+Mono/Macro subcluster, which indicates a pivotal role in immune regulation and potential therapeutic targeting. In this research, single-cell RNA sequencing datasets are utilized to analyze the immune cell landscape in sepsis, highlighting significant variations in the distribution of monocyte/macrophage populations. The findings uncover cell clusters with high expression of MYOF that are intricately linked to survival outcomes, delving into the detailed cellular dynamics. This study provides new insights into the immunodynamics of sepsis, emphasizing potential targets for therapeutic intervention. image"

基金机构："National Natural Science Foundation of China; Natural Science Foundation Project of Chongqing [CSTB2022NSCQ-MSX0058, CSTB2022NSCQ-BHX0711, CSTB2022NSCQ-BHX0670, CSTB2022NSCQ-MSX0135]; Medical Research Projects of Chongqing [2023ZDXM003]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University; [82302430]; [82172135]; [81701950]; [81971880]"

基金资助正文："The authors express their gratitude to Mr. Jiezhong Guan (Sun Yat-sen University) for his support in bioinformatic analysis. This study was supported by the National Natural Science Foundation of China (No. 82302430, No. 82172135, No. 81701950 and No. 81971880), Natural Science Foundation Project of Chongqing (CSTB2022NSCQ-MSX0058, CSTB2022NSCQ-BHX0711, CSTB2022NSCQ-BHX0670, and CSTB2022NSCQ-MSX0135), Medical Research Projects of Chongqing (No. 2023ZDXM003) and Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University."