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Dec 3, 2024

Protze Lab Identifies First Cell Surface Marker for Human Cardiac Pacemaker Cells

Research Highlights
Lim_et_al._2024
Amos Lim and Matthew Chang, first and co-author on the study and graduate students in the Protze lab
Microscopic images of heart cells reveal SAN cells are uniquely marked by CD34 (red). DNA (blue) is visible in all cells, while NKX2-5 (green) highlights non-SAN cells, showcasing the distinct identity of SAN cells.

First posted on UHN's newsfeed on November 27, 2024

The sinoatrial node (SAN), a cluster of approximately 10,000 specialized heart cells (cardiomyocytes) called pacemaker cells, generates every heartbeat throughout a human’s lifetime. Developing SAN cell models from human stem cells has become an invaluable tool for studying these cells and related disorders.

A recent breakthrough from the McEwen Stem Cell Institute at UHN (McEwen) could transform how researchers develop models to study the SAN.

Using cutting-edge single-cell and single-nuclei RNA sequencing, the McEwen team created a detailed profile of genes expressed in fetal SAN cells and SAN-like pacemaker cells (SANLPCs). This analysis led to the discovery of the first cell surface marker for SAN cells–CD34.

CD34, absent in other cardiomyocytes, allows researchers to distinguish SANLPCs from other cells in stem cell-derived differentiation cultures.  Moreover, as CD34 is located on the cell surface, researchers can identify SANLPCs in these cultures without having to rely on specially engineered cell lines called reporter lines.

These findings not only promise to refine SAN models, but also unlock new possibilities for treating SAN-related disorders. By enabling the isolation of SANLPCs from stem cell cultures, this breakthrough advances the development of biological pacemakers that one day could be used to treat patients with SAN disorders.

The first author of this study is Amos Lim, Graduate Student at McEwen Stem Cell Institute.

A co-author of this study Dr. Michael Laflamme, Senior Scientist at McEwen Stem Cell Institute, is the Canada Research Chair in Cardiovascular Regenerative Medicine.

The senior author of this study is Dr. Stephanie Protze, a Scientist at McEwen Stem Cell Institute and an Assistant Professor at the Department of Molecular Genetics at the University of Toronto.

This work was supported by the Canadian Stem Cell Network, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Canadian Research Chairs Program, BlueRock Therapeutics LP, and UHN Foundation.