Single-Cell Proteomics Reveals Specific Cellular Subtypes in Cardiomyocytes Derived From Human iPSCs and Adult Hearts.

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Publication Year:
2025
Authors:
Lizhuo Ai, Aleksandra Binek, Vladimir Zhemkov, Jae Hyung Cho, Ali Haghani, Simion Kreimer, Edo Israely, Madelyn Arzt, Blandine Chazarin, Niveda Sundararaman, Jesse G Meyer, Arun Sharma, Eduardo Marban, Clive N Svendsen, Jennifer E Van Eyk
PubMed ID:
39855627
Funding Grants:
Public Summary:
Researchers used single-cell proteomics to study protein levels in human stem cells, stem cell–derived heart cells, and adult heart cells. They measured over 700 proteins in each cell and found unique groups within these populations. For example, some stem cells at the edges of colonies had higher levels of certain markers. In heart cells, two main types appeared: stem cell–derived ones relied more on sugar metabolism, while adult heart cells mainly used fat metabolism. Surprisingly, a few rare cells showed markers of both heart and nerve cells, hinting at a possible new hybrid cell type in the human heart.
Scientific Abstract:
Single-cell proteomics was performed on human induced pluripotent stem cells (iPSCs), iPSC-derived cardiomyocytes, and adult cardiomyocytes. More than 700 proteins could be simultaneously measured in each cell revealing unique subpopulations. A subset of iPSCs expressed higher levels of Lin28a and Tra-1-60 towards the outer edge of cell colonies. In the cardiomyocytes, two distinct populations were found that exhibited complementary metabolic profiles. Cardiomyocytes from iPSCs showed a glycolysis profile while adult cardiomyocytes were enriched in proteins involved with fatty acid metabolism. Interestingly, rare single cells also co-expressed markers of both cardiac and neuronal lineages, suggesting there may be a novel hybrid cell type in the human heart.