CD151 expression marks atrial- and ventricular- differentiation from human induced pluripotent stem cells

Area of Science:

• Stem Cell Biology
• Cardiovascular Research
• Cell Differentiation

Background:

• Current protocols for differentiating human induced pluripotent stem cells (hiPSCs) yield heterogeneous cardiomyocytes (CMs).
• Chamber-specific CM selection using cell surface antigens is valuable, but a marker distinguishing hiPSC-derived atrial CMs (ACMs) from ventricular CMs (VCMs) is lacking.

Purpose of the Study:

• To develop a method for obtaining functional hiPSC-derived ACMs and VCMs.
• To identify a cell surface marker for distinguishing between hiPSC-derived ACMs and VCMs.

Main Methods:

• Investigated CD151 expression in differentiating hiPSCs.
• Utilized Notch signaling modulation and CD151 expression for cell population selection.
• Assessed cell identity through gene expression and electrophysiology.

Main Results:

• ACMs are enriched in the CD151^low population, correlating with Notch4 expression.
• Notch signaling inhibition and CD151^low selection efficiently generated ACMs.
• VCMs are enriched in the CD151^high population, exhibiting ventricular characteristics.

Conclusions:

• CD151 expression serves as a reliable marker to distinguish hiPSC-derived ACMs and VCMs.
• This approach enables the efficient production of high-quality, chamber-specific cardiomyocytes.
• The findings support the development of hiPSC-derived chamber-specific disease models.