Journal Article

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

Xu, Ji-Ying, Chen, Hai-Bin, Li, Yu-Hui, Tang, Qi-Dong, Xie, Jia-Jia, Li, Xiao-Wei, Yang, Yao-Lin

2024

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Angiology / Animals / Blood Transfusion Medicine / Cardiac resident macrophages / Cardiac Surgery / Cardiology / Cardiomyocytes / Cardiovascular disease / Cardiovascular diseases / Care and treatment / Case-Control Studies / Cell differentiation / Cells / Cellular Microenvironment / Clustering / Complications and side effects / Congestive heart failure / Data analysis / Databases, Genetic / Datasets / Epigenetic inheritance / Epigenetics / Gene expression / Gene Expression Profiling / Gene Expression Regulation / Genetic aspects / Genomics / Heart diseases / Heart failure / Heart Failure - genetics / Heart Failure - immunology / Heart Failure - metabolism / Humans / Immune microenvironment / Immune response / Immunology / Internal Medicine / Lymphocytes T / Macrophages / Macrophages - immunology / Macrophages - metabolism / Medicine / Medicine & Public Health / Microenvironments / Myeloid cells / Myogenesis / Neutrophils / Population studies / RNA modification / RNA Processing, Post-Transcriptional / Single-Cell Analysis / Therapeutic targets / Transcriptome / Transcriptomics / Transfer RNA / Writers of RNA modification / WRM score