The cellular prion protein identifies bipotential cardiomyogenic progenitors

Area of Science:

• Cardiovascular Biology
• Stem Cell Biology
• Developmental Biology

Background:

• Specific surface markers for cardiomyocytes and their progenitors are lacking, hindering stem cell-based transplantation therapies.
• Identifying these markers can improve understanding of cardiac cell differentiation mechanisms.

Purpose of the Study:

• To identify effective surface markers for isolating nascent cardiomyocytes and cardiomyogenic progenitors.
• To characterize the differentiation potential of cells identified by these markers.

Main Methods:

• Flow cytometry was used to analyze surface expression of cellular prion protein (PrP) and intracellular myosin heavy chain (Myhc) in embryonic stem cells.
• Sorted cells were assessed for their differentiation capacity.

Main Results:

• PrP-positive (PrP+) cells from beating embryoid bodies contained nascent Myhc-positive (Myhc+) cardiomyocytes.
• Cultured PrP+ cells differentiated into functional cardiac troponin I-positive cardiomyocytes with atrial or ventricular identity.
• Combining PrP with platelet-derived growth factor receptor alpha (PDGFRα) identified an earlier cardiomyogenic population (PrP+PDGFRα+ or PRα cells) in prebeating embryoid bodies.

Conclusions:

• PrP marks a population of bipotential cardiomyogenic progenitor cells.
• These progenitor cells can differentiate into either cardiac or smooth muscle cells.
• PrP+PDGFRα+ cells express key cardiac transcription factors and are bipotential, representing an early cardiomyogenic population.