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

Author

Listed:
  • Amos A. Lim

    (University Health Network
    University of Toronto)

  • Delaram Pouyabahar

    (University of Toronto
    University of Toronto)

  • Mishal Ashraf

    (University of British Columbia and St. Paul’s Hospital
    University of British Columbia)

  • Kate Huang

    (University of British Columbia and St. Paul’s Hospital
    University of British Columbia)

  • Michelle Lohbihler

    (University Health Network
    University of Toronto)

  • Brandon M. Murareanu

    (University Health Network
    University of Toronto)

  • Matthew L. Chang

    (University Health Network
    University of Toronto)

  • Maggie Kwan

    (University Health Network)

  • Faisal J. Alibhai

    (University Health Network)

  • Thinh Tran

    (University of Toronto
    University of Toronto
    Memorial Sloan Kettering Cancer Center)

  • Amine Mazine

    (University Health Network
    University of Toronto
    University of Toronto)

  • Michael A. Laflamme

    (University Health Network
    University of Toronto)

  • Gary D. Bader

    (University of Toronto
    University of Toronto
    University of Toronto
    University Health Network)

  • Zachary Laksman

    (University of British Columbia and St. Paul’s Hospital
    University of British Columbia
    University of British Columbia
    University of British Columbia)

  • Stephanie Protze

    (University Health Network
    University of Toronto)

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.

Suggested Citation

  • 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. , 2024. "Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54337-4
    DOI: 10.1038/s41467-024-54337-4
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    References listed on IDEAS

    as
    1. Dandan Liang & Jinfeng Xue & Li Geng & Liping Zhou & Bo Lv & Qiao Zeng & Ke Xiong & Huixing Zhou & Duanyang Xie & Fulei Zhang & Jie Liu & Yi Liu & Li Li & Jian Yang & Zhigang Xue & Yi-Han Chen, 2021. "Cellular and molecular landscape of mammalian sinoatrial node revealed by single-cell RNA sequencing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Nora Linscheid & Sunil Jit R. J. Logantha & Pi Camilla Poulsen & Shanzhuo Zhang & Maren Schrölkamp & Kristoffer Lihme Egerod & Jonatan James Thompson & Ashraf Kitmitto & Gina Galli & Martin J. Humphri, 2019. "Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking," Nature Communications, Nature, vol. 10(1), pages 1-19, December.
    3. Kazumasa Kanemaru & James Cranley & Daniele Muraro & Antonio M. A. Miranda & Siew Yen Ho & Anna Wilbrey-Clark & Jan Patrick Pett & Krzysztof Polanski & Laura Richardson & Monika Litvinukova & Natsuhik, 2023. "Spatially resolved multiomics of human cardiac niches," Nature, Nature, vol. 619(7971), pages 801-810, July.
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