Abstract: Human pluripotent stem cells (hPSCs) can generate specific cell types for therapeutic applications. Cell therapy often requires billions of cells for transplantation, so it is critical to maximize the potential of differentiation to optimize both quantity and quality. Cardiomyocytes are commonly induced in static culture with limited expandability. In this study, we explored the impact of cell adhesion remodeling on hPSC cell fate determination. We reveal that cell dissociation at critical time points drives cardiac cell fate even without traditional cardiac inducers. Cardiac fate is specified while cells proliferate continuously. Cell adhesion remodeling leads to a 10-fold increase in the yield of high-purity cardiomyocytes compared to traditional static culture. Transcriptomic analysis suggests that cell adhesion remodeling enhances the expression of critical cardiac genes associated with maturation. This study highlights that cell adhesion remodeling significantly impacts cell fate during in vitro differentiation. Our study provides an ideal method for high-yield, high-purity cardiomyocyte production, and offers a useful strategy for generating other cell types through directed differentiation.
Funding Source: This work was supported by the University of Macau (File No. MYRG-GRG2023-00137-FHS-UMDF) and by the Science and Technology Development Fund, Macau SAR (File No. 0010/2023/AKP and 0073/2023/ITP2).
