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Updated: Nov 2, 2025
Isolation of Macrophage Subsets and Stromal Cells from Human and Mouse Myocardial Specimens
Published on: December 17, 2019
Single-cell transcriptomic analyses of cardiac immune cells reveal that Rel-driven CD72-positive macrophages induce
Shi-Hao Ni1,2,3, Jin-Dong Xu4, Shu-Ning Sun1,2,3
1The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China.
Aims:
The goal of our study was to investigate the heterogeneity of cardiac macrophages (CMφs) in mice with transverse aortic constriction (TAC) via single-cell sequencing and identify a subset of macrophages associated with heart injury.
Methods And Results:
We selected all CMφs from CD45+ cells using single-cell mRNA sequencing data. Through dimension reduction, clustering, and enrichment analyses, CD72hi CMφs were identified as a subset of pro-inflammatory macrophages. The pseudo-time trajectory and ChIP-Seq analyses identified Rel as the key transcription factor that induces CD72hi CMφ differentiation. Rel KD and Rel-/- bone marrow chimaera mice subjected to TAC showed features of mitigated cardiac injury, including decreased levels of cytokines and ROS, which prohibited cardiomyocyte death. The transfer of adoptive Rel-overexpressing monocytes and CD72hi CMφ injection directly aggravated heart injury in the TAC model. The CD72hi macrophages also exerted pro-inflammatory and cardiac injury effects associated with myocardial infarction. In humans, patients with heart failure exhibit increased CD72hi CMφ levels following dilated cardiomyopathy and ischaemic cardiomyopathy.
Conclusion:
Bone marrow-derived, Rel-mediated CD72hi macrophages play a pro-inflammatory role, induce cardiac injury and, thus, may serve as a therapeutic target for multiple cardiovascular diseases.
Insights
Researchers identified a specific type of cardiac macrophage, CD72hi macrophages, that worsen heart injury by promoting inflammation. Targeting these Rel-mediated macrophages could offer a new therapeutic strategy for cardiovascular diseases.
Area of Science:
- Immunology
- Cardiovascular Biology
- Molecular Biology
Background:
- Cardiac macrophages (CMφs) play critical roles in heart homeostasis and disease.
- Understanding macrophage heterogeneity is crucial for developing targeted therapies for cardiovascular conditions.
Purpose of the Study:
- To investigate the heterogeneity of cardiac macrophages in a mouse model of heart injury.
- To identify specific macrophage subsets involved in cardiac damage and inflammation.
Main Methods:
- Single-cell mRNA sequencing was employed to analyze cardiac macrophages from mice subjected to transverse aortic constriction (TAC).
- Bioinformatic analyses including dimension reduction, clustering, and enrichment were performed.
- ChIP-Seq and pseudo-time trajectory analyses identified key transcription factors.
Main Results:
- A pro-inflammatory subset of cardiac macrophages, termed CD72hi CMφs, was identified.
- The transcription factor Rel was identified as a key driver of CD72hi CMφ differentiation.
- Reducing Rel expression or depleting CD72hi CMφs mitigated cardiac injury in TAC mice.
- Increased CD72hi CMφ levels were observed in human heart failure patients.
Conclusions:
- Rel-mediated CD72hi macrophages contribute to cardiac inflammation and injury.
- These macrophages represent a potential therapeutic target for cardiovascular diseases like heart failure.
