Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes
Abstract The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved. Particularly, no cell surface m...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54337-4 |
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| author | Amos A. Lim Delaram Pouyabahar Mishal Ashraf Kate Huang Michelle Lohbihler Brandon M. Murareanu Matthew L. Chang Maggie Kwan Faisal J. Alibhai Thinh Tran Amine Mazine Michael A. Laflamme Gary D. Bader Zachary Laksman Stephanie Protze |
| author_facet | Amos A. Lim Delaram Pouyabahar Mishal Ashraf Kate Huang Michelle Lohbihler Brandon M. Murareanu Matthew L. Chang Maggie Kwan Faisal J. Alibhai Thinh Tran Amine Mazine Michael A. Laflamme Gary D. Bader Zachary Laksman Stephanie Protze |
| author_sort | Amos A. Lim |
| collection | DOAJ |
| description | Abstract The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved. Particularly, no cell surface marker to identify and isolate sinoatrial node pacemaker cells has been reported. Here we use single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell-derived sinoatrial node cells to reveal that they consist of three subtypes of pacemaker cells: Core Pacemaker, Sinus Venosus, and Transitional Cells. Our study identifies a host of sinoatrial node pacemaker markers including MYH11, BMP4, and the cell surface antigen CD34. We demonstrate that sorting for CD34+ cells from stem cell differentiation cultures enriches for sinoatrial node cells exhibiting a functional pacemaker phenotype. This sinoatrial node pacemaker cell surface marker is highly valuable for stem cell-based disease modeling, drug discovery, cell replacement therapies, and the targeted delivery of therapeutics to sinoatrial node cells in vivo using antibody-drug conjugates. |
| format | Article |
| id | doaj-art-f73cd776dca1419b9175c6eed03fe7ce |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f73cd776dca1419b9175c6eed03fe7ce2024-12-01T12:33:55ZengNature PortfolioNature Communications2041-17232024-11-0115112210.1038/s41467-024-54337-4Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytesAmos A. Lim0Delaram Pouyabahar1Mishal Ashraf2Kate Huang3Michelle Lohbihler4Brandon M. Murareanu5Matthew L. Chang6Maggie Kwan7Faisal J. Alibhai8Thinh Tran9Amine Mazine10Michael A. Laflamme11Gary D. Bader12Zachary Laksman13Stephanie Protze14McEwen Stem Cell Institute, University Health NetworkDepartment of Molecular Genetics, University of TorontoCentre for Heart and Lung Innovation, University of British Columbia and St. Paul’s HospitalCentre for Heart and Lung Innovation, University of British Columbia and St. Paul’s HospitalMcEwen Stem Cell Institute, University Health NetworkMcEwen Stem Cell Institute, University Health NetworkMcEwen Stem Cell Institute, University Health NetworkMcEwen Stem Cell Institute, University Health NetworkMcEwen Stem Cell Institute, University Health NetworkDepartment of Molecular Genetics, University of TorontoMcEwen Stem Cell Institute, University Health NetworkMcEwen Stem Cell Institute, University Health NetworkDepartment of Molecular Genetics, University of TorontoCentre for Heart and Lung Innovation, University of British Columbia and St. Paul’s HospitalMcEwen Stem Cell Institute, University Health NetworkAbstract The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved. Particularly, no cell surface marker to identify and isolate sinoatrial node pacemaker cells has been reported. Here we use single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell-derived sinoatrial node cells to reveal that they consist of three subtypes of pacemaker cells: Core Pacemaker, Sinus Venosus, and Transitional Cells. Our study identifies a host of sinoatrial node pacemaker markers including MYH11, BMP4, and the cell surface antigen CD34. We demonstrate that sorting for CD34+ cells from stem cell differentiation cultures enriches for sinoatrial node cells exhibiting a functional pacemaker phenotype. This sinoatrial node pacemaker cell surface marker is highly valuable for stem cell-based disease modeling, drug discovery, cell replacement therapies, and the targeted delivery of therapeutics to sinoatrial node cells in vivo using antibody-drug conjugates.https://doi.org/10.1038/s41467-024-54337-4 |
| spellingShingle | Amos A. Lim Delaram Pouyabahar Mishal Ashraf Kate Huang Michelle Lohbihler Brandon M. Murareanu Matthew L. Chang Maggie Kwan Faisal J. Alibhai Thinh Tran Amine Mazine Michael A. Laflamme Gary D. Bader Zachary Laksman Stephanie Protze Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes Nature Communications |
| title | Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes |
| title_full | Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes |
| title_fullStr | Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes |
| title_full_unstemmed | Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes |
| title_short | Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes |
| title_sort | single cell transcriptome analysis reveals cd34 as a marker of human sinoatrial node pacemaker cardiomyocytes |
| url | https://doi.org/10.1038/s41467-024-54337-4 |
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