单细胞转录组学揭示了 RNA 修饰介导的免疫微环境的书写者和心力衰竭中心肌驻留的 Macro-MYL2 巨噬细胞。

Single-cell transcriptomics reveals writers of RNA modification-mediated immune microenvironment and cardiac resident Macro-MYL2 macrophages in heart failure.

机构信息

First Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospi-tal of Jinan University, NO. 466, Xingang Middle Road, Haizhu District, Guangzhou City, China.

出版信息

BMC Cardiovasc Disord. 2024 Aug 16;24(1):432. doi: 10.1186/s12872-024-04080-x.

DOI:10.1186/s12872-024-04080-x

PMID:39152369

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11328403/

Abstract

BACKGROUND

Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown.

METHODS

We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored.

RESULTS

Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics.

CONCLUSION

Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.

摘要

背景

心力衰竭（HF）是由心脏超负荷和损伤引起的，与高死亡率相关。RNA 修饰写手（WRMs）在调节免疫反应和心血管疾病相关的表观遗传过程中发挥着关键作用。然而，这些写手在 HF 免疫微环境中的潜在作用尚不清楚。

方法

我们使用数据集 GSE145154 和 GSE141910 全面描述了 28 个 WRMs 的表达情况，以绘制 HF 患者心脏免疫微环境图谱。根据 WRMs 的表达情况，对数据集中的免疫细胞进行评分。

结果

单细胞转录组学分析（GSE145154）显示 HF 存在免疫失调，HF 和非 HF（NHF）样本中的 WRMs 在免疫细胞中差异表达。WRM 评分免疫细胞与免疫反应呈正相关，高 WRM 评分组表现出免疫细胞浸润增加。WRMs 参与 T 细胞和髓样细胞的分化。与 NHF 组相比，HF 组 T 细胞和髓样细胞亚型的 WRM 评分显著降低。我们在心脏中发现了一种与肌生成相关的驻留巨噬细胞群体 Macro-MYL2，其特征是肌节结构基因（MYL2、TNNI3、TNNC1、TCAP 和 TNNT2）表达增加，并受 TRMT10C 调节。根据 WRM 表达模式，转录组学数据（GSE141910）确定了两种不同的 HF 样本聚类，每个聚类都具有独特的功能富集和免疫特征。