Proteomic variation in heart tissues

Induced pluripotent stem cells, or iPSCs, can be used to model tissues and disorders, such as heart diseases. However, the human heart is complex, with several regions and cell types. Therefore, analyzing single cardiac cells can be challenging.

Lizhuo Ai, Aleksandra Binek and Vladimir Zhemkov of the Cedars-Sinai Medical Center and a team in the U.S. used this approach to analyze heart cells throughout various stages of development. They published their findings in Molecular & Cellular Proteomics. The authors differentiated iPSCs into cardiomyocytes, the muscle cells of the heart, and analyzed their proteome at various time points using mass spectrometry.

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The team detected proteomic differences between groups of iPSC-derived cardiomyocytes, or iCMs, at the end of their three-week differentiation period, suggesting that they had developed into multiple cell subtypes. Many differentially expressed proteins between two of these subtypes functioned in extracellular vesicles, called exosomes, which transport biomolecules such as DNA and proteins to other cells. They also compared iCMs to those isolated from adult human hearts, or aCMs. They found the two cell types shared many proteins involved in muscle function, but that aCMs had a higher proportion of mitochondrial proteins, suggesting that iCMs are metabolically immature.

Furthermore, detailed analysis revealed that a few human adult heart cells expressed markers that traditionally identify heart and brain cells, which may represent a newly discovered cell type. These results could mean that heart cells are more diverse than scientists originally thought and could underlie some functions such as exosome formation. The ability of iCMs to recreate much of the cardiomyocyte proteome, combined with the diversity of tissues they produce, make iPSCs appealing candidates for studying and treating human heart diseases.