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Published on: September 2, 2021
Genetic Lineage Tracing of Pericardial Cavity Macrophages in the Injured Heart
Hengwei Jin1, Kuo Liu2, Xiuzhen Huang1
1State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (H.J., X.H., J.M., B.Z.), University of Chinese Academy of Sciences, China.
Insights
Gata6+ pericardial macrophages (GPCMs) do not significantly infiltrate injured hearts after myocardial infarction (MI) or prevent cardiac fibrosis. This study highlights the need for precise genetic tools to investigate cell functions in vivo.
Area of Science:
- Cardiovascular Biology
- Immunology
- Regenerative Medicine
Background:
- Macrophages are crucial for cardiac repair post-myocardial infarction (MI).
- Gata6+ cavity macrophages in the pericardial space were hypothesized to aid cardiac repair.
- Direct genetic evidence for their role in myocardial repair was lacking.
Purpose of the Study:
- To genetically label and track Gata6+ pericardial macrophages (GPCMs) in vivo.
- To investigate the functional role of GPCMs in cardiac repair after MI.
- To determine if GPCMs prevent cardiac fibrosis or improve cardiac function post-MI.
Main Methods:
- Utilized dual recombinases (Cre and Dre) for specific GPCM labeling.
- Generated genetic systems for targeted ablation of GPCMs (DTR expression or Gata6 knockout).
- Studied GPCM behavior and function in a pericardium-intact MI model.
Main Results:
- The genetic system specifically and efficiently targeted GPCMs.
- Lineage tracing showed GPCMs accumulated on the heart surface, not penetrating the myocardium.
- GPCM ablation or Gata6 knockout did not alter cardiac fibrosis or function post-MI.
Conclusions:
- Gata6+ pericardial macrophages exhibit minimal invasion into the injured heart post-MI.
- GPCMs do not appear to prevent cardiac fibrosis or provide reparative function.
- Emphasizes the importance of specific genetic tools for in vivo cell fate and function studies.
Background:
Macrophages play an important role in cardiac repair after myocardial infarction (MI). In addition to the resident macrophages and blood-derived monocytes, Gata6+ cavity macrophages located in the pericardial space were recently reported to relocate to the injured myocardium and prevent cardiac fibrosis. However, there is no direct genetic evidence to support it.
Methods:
We used dual recombinases (Cre and Dre) to specifically label Gata6+ pericardial macrophages (GPCMs) in vivo. For functional study, we generated genetic systems to specifically ablate GPCMs by induced expression of DTR (diphtheria toxin receptor) or knockout of Gata6 (GATA binding protein 6) gene in GPCMs. We used these genetic systems to study GPCMs in pericardium intact MI model.
Results:
Dual recombinases-mediated genetic system targeted GPCMs specifically and efficiently. Lineage tracing study revealed accumulation of GPCMs on the surface of MI heart without deep penetration into the myocardium. We did not detect significant change of cardiac fibrosis or function of MI hearts after cell ablation or Gata6 knockout in GPCMs.
Conclusions:
GPCMs minimally invade the injured heart after MI. Nor do they prevent cardiac fibrosis and exhibit reparative function on injured heart. This study also underlines the importance of using specific genetic tool for studying in vivo cell fates and functions.
