Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury
Abstract The immune system coordinates the response to cardiac injury and controls regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Adult mice and humans lack the ability to fully recover while adult zebrafish spontaneo...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07315-x |
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| author | Eric Cortada Jun Yao Yu Xia Friederike Dündar Paul Zumbo Boris Yang Alfonso Rubio-Navarro Björn Perder Miaoyan Qiu Anthony M. Pettinato Edwin A. Homan Lisa Stoll Doron Betel Jingli Cao James C. Lo |
| author_facet | Eric Cortada Jun Yao Yu Xia Friederike Dündar Paul Zumbo Boris Yang Alfonso Rubio-Navarro Björn Perder Miaoyan Qiu Anthony M. Pettinato Edwin A. Homan Lisa Stoll Doron Betel Jingli Cao James C. Lo |
| author_sort | Eric Cortada |
| collection | DOAJ |
| description | Abstract The immune system coordinates the response to cardiac injury and controls regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Adult mice and humans lack the ability to fully recover while adult zebrafish spontaneously regenerate after heart injury. Here we profile the inflammatory response to heart cryoinjury in zebrafish and coronary artery ligation in mouse using single cell transcriptomics. We interrogate the extracardiac reaction to cardiomyocyte necrosis to assess the specific peripheral tissue and immune cell reaction to chronic stress. Cardiac macrophages play a critical role in determining tissue homeostasis by healing versus scarring. We identify distinct transcriptional clusters of monocytes/macrophages (mono/Mϕ) in each species and find analogous pairs in zebrafish and mice. However, the reaction to myocardial injury is largely disparate between mice and zebrafish. The dichotomous response to heart damage between the murine and zebrafish mono/Mϕ and/or the presence of distinct zebrafish mono/Mϕ subtypes may underlie the impaired regenerative process in adult mammals and humans. Our study furnishes a direct cross-species comparison of immune responses between regenerative and profibrotic myocardial injury models, providing a useful resource to the fields of regenerative biology and cardiovascular research. |
| format | Article |
| id | doaj-art-db76a07b84b146119dc711b8764a9b4f |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-db76a07b84b146119dc711b8764a9b4f2024-12-08T12:41:26ZengNature PortfolioCommunications Biology2399-36422024-12-017112010.1038/s42003-024-07315-xCross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injuryEric Cortada0Jun Yao1Yu Xia2Friederike Dündar3Paul Zumbo4Boris Yang5Alfonso Rubio-Navarro6Björn Perder7Miaoyan Qiu8Anthony M. Pettinato9Edwin A. Homan10Lisa Stoll11Doron Betel12Jingli Cao13James C. Lo14Division of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Weill Cornell MedicineCardiovascular Research Institute, Weill Cornell MedicineCardiovascular Research Institute, Weill Cornell MedicineApplied Bioinformatics Core, Weill Cornell MedicineApplied Bioinformatics Core, Weill Cornell MedicineDivision of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Weill Cornell MedicineDivision of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Weill Cornell MedicineCardiovascular Research Institute, Weill Cornell MedicineCardiovascular Research Institute, Weill Cornell MedicineDivision of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Weill Cornell MedicineDivision of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Weill Cornell MedicineDivision of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Weill Cornell MedicineApplied Bioinformatics Core, Weill Cornell MedicineCardiovascular Research Institute, Weill Cornell MedicineDivision of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Weill Cornell MedicineAbstract The immune system coordinates the response to cardiac injury and controls regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Adult mice and humans lack the ability to fully recover while adult zebrafish spontaneously regenerate after heart injury. Here we profile the inflammatory response to heart cryoinjury in zebrafish and coronary artery ligation in mouse using single cell transcriptomics. We interrogate the extracardiac reaction to cardiomyocyte necrosis to assess the specific peripheral tissue and immune cell reaction to chronic stress. Cardiac macrophages play a critical role in determining tissue homeostasis by healing versus scarring. We identify distinct transcriptional clusters of monocytes/macrophages (mono/Mϕ) in each species and find analogous pairs in zebrafish and mice. However, the reaction to myocardial injury is largely disparate between mice and zebrafish. The dichotomous response to heart damage between the murine and zebrafish mono/Mϕ and/or the presence of distinct zebrafish mono/Mϕ subtypes may underlie the impaired regenerative process in adult mammals and humans. Our study furnishes a direct cross-species comparison of immune responses between regenerative and profibrotic myocardial injury models, providing a useful resource to the fields of regenerative biology and cardiovascular research.https://doi.org/10.1038/s42003-024-07315-x |
| spellingShingle | Eric Cortada Jun Yao Yu Xia Friederike Dündar Paul Zumbo Boris Yang Alfonso Rubio-Navarro Björn Perder Miaoyan Qiu Anthony M. Pettinato Edwin A. Homan Lisa Stoll Doron Betel Jingli Cao James C. Lo Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury Communications Biology |
| title | Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury |
| title_full | Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury |
| title_fullStr | Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury |
| title_full_unstemmed | Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury |
| title_short | Cross-species single-cell RNA-seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury |
| title_sort | cross species single cell rna seq analysis reveals disparate and conserved cardiac and extracardiac inflammatory responses upon heart injury |
| url | https://doi.org/10.1038/s42003-024-07315-x |
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