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Updated: Jul 2, 2025
High Efficiency Differentiation of Human Pluripotent Stem Cells to Cardiomyocytes and Characterization by Flow Cytometry
Published on: September 23, 2014
CD151 expression marks atrial- and ventricular- differentiation from human induced pluripotent stem cells
Misato Nakanishi-Koakutsu1,2,3,4, Kenji Miki5,6,7,8, Yuki Naka1,2
1Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606-8507, Japan.
Insights
Researchers identified CD151 as a cell surface marker to distinguish human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes. This discovery enables efficient generation of chamber-specific cells for disease modeling.
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 CD151low population, correlating with Notch4 expression.
- Notch signaling inhibition and CD151low selection efficiently generated ACMs.
- VCMs are enriched in the CD151high 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.
Abstract:
Current differentiation protocols for human induced pluripotent stem cells (hiPSCs) produce heterogeneous cardiomyocytes (CMs). Although chamber-specific CM selection using cell surface antigens enhances biomedical applications, a cell surface marker that accurately distinguishes between hiPSC-derived atrial CMs (ACMs) and ventricular CMs (VCMs) has not yet been identified. We have developed an approach for obtaining functional hiPSC-ACMs and -VCMs based on CD151 expression. For ACM differentiation, we found that ACMs are enriched in the CD151low population and that CD151 expression is correlated with the expression of Notch4 and its ligands. Furthermore, Notch signaling inhibition followed by selecting the CD151low population during atrial differentiation leads to the highly efficient generation of ACMs as evidenced by gene expression and electrophysiology. In contrast, for VCM differentiation, VCMs exhibiting a ventricular-related gene signature and uniform action potentials are enriched in the CD151high population. Our findings enable the production of high-quality ACMs and VCMs appropriate for hiPSC-derived chamber-specific disease models and other applications.
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