Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes

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 and Stephanie Protze ()
Additional contact information
Amos A. Lim: University Health Network
Delaram Pouyabahar: University of Toronto
Mishal Ashraf: University of British Columbia and St. Paul’s Hospital
Kate Huang: University of British Columbia and St. Paul’s Hospital
Michelle Lohbihler: University Health Network
Brandon M. Murareanu: University Health Network
Matthew L. Chang: University Health Network
Maggie Kwan: University Health Network
Faisal J. Alibhai: University Health Network
Thinh Tran: University of Toronto
Amine Mazine: University Health Network
Michael A. Laflamme: University Health Network
Gary D. Bader: University of Toronto
Zachary Laksman: University of British Columbia and St. Paul’s Hospital
Stephanie Protze: University Health Network

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54337-4

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