Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes
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<sup>+</sup> 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.
Authors
- Gary D. Bader (ORCID: https://orcid.org/0000-0003-0185-8861)
- Stephanie Protze (ORCID: https://orcid.org/0000-0002-7993-3780)
- Mishal Ashraf (ORCID: https://orcid.org/0000-0002-3096-7736)
- Maggie Kwan
- Delaram Pouyabahar (ORCID: https://orcid.org/0000-0002-8686-8067)
- Matthew L. Chang (ORCID: https://orcid.org/0000-0003-3184-3388)
- Brandon M. Murareanu (ORCID: https://orcid.org/0000-0002-2517-2517)
- Kate Huang (ORCID: https://orcid.org/0000-0002-6515-5324)
- Amine Mazine (ORCID: https://orcid.org/0000-0001-9086-9823)
- Zachary Laksman (ORCID: https://orcid.org/0000-0002-7790-541X)
- Michael A. Laflamme (ORCID: https://orcid.org/0000-0001-5908-880X)
- Faisal J. Alibhai (ORCID: https://orcid.org/0000-0002-8145-4682)
- Thinh Huy Tran (ORCID: https://orcid.org/0009-0005-6601-9825)
- Michelle Lohbihler
- Amos A. Lim
Institutions
- University Health Network (CA)
- Memorial Sloan Kettering Cancer Center (US)
- University of British Columbia (CA)
- University of Toronto (CA)
- Lunenfeld-Tanenbaum Research Institute (CA)
- St. Paul's Hospital (CA)
- Princess Margaret Cancer Centre (CA)
- Sinai Health System (CA)
- Molecular Oncology (United States) (US)
- Stem Cell Network (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1038/s41467-024-54337-4
- Citations
- 8
- Primary Topic
- Congenital heart defects research
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- Canadian Institutes of Health Research