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

Area of Science:

• Proteomics
• Stem Cell Biology
• Cardiology

Background:

• Understanding cellular heterogeneity is crucial for stem cell research and cardiac medicine.
• Previous studies lacked high-resolution proteomic data at the single-cell level for these cell types.

Purpose of the Study:

• To characterize protein expression profiles in human induced pluripotent stem cells (iPSCs) and their differentiated cardiomyocytes at single-cell resolution.
• To identify distinct cellular subpopulations and their unique molecular characteristics.
• To explore potential novel cell types within the human heart.

Main Methods:

• Single-cell proteomics was employed to simultaneously measure over 700 proteins per cell.
• Analysis was conducted on human induced pluripotent stem cells (iPSCs), iPSC-derived cardiomyocytes, and adult cardiomyocytes.

Main Results:

• Over 700 proteins were quantified per cell, revealing significant subpopulations.
• A subset of iPSCs showed specific surface marker expression (Lin28a, Tra-1-60) at colony edges.
• Two distinct cardiomyocyte populations emerged with complementary metabolic profiles: iPSC-cardiomyocytes utilized glycolysis, while adult cardiomyocytes relied on fatty acid metabolism.
• Rare single cells exhibited co-expression of cardiac and neuronal lineage markers.

Conclusions:

• Single-cell proteomics effectively delineates cellular heterogeneity in iPSCs and cardiomyocytes.
• Metabolic plasticity exists between iPSC-derived and adult cardiomyocytes.
• The discovery of rare cells co-expressing cardiac and neuronal markers suggests a potential novel hybrid cell type in the human heart.