Data-driven Maturity Level Evaluation for Cardiomyocytes derived from Human Pluripotent Stem Cells (Invited Paper)

Cardiovascular diseases are one of the leading causes of death in the world. The capability to direct the differentiation of human pluripotent stem cells (hPSCs) into functional cardiomyocytes (CMs) provides excellent opportunities for disease modeling and novel cell-based cardiac therapies. However, current hPSC-derived cardiomyocytes (hPSC-CMs) remain largely immature, limiting experimental and clinical uses. New insights into the maturation process of adult-like hPSC-CMs are critical. In this paper, we developed a data-driven pipeline to quantify cell maturity, based on gene expression input spanning different stages of cardiac development. First, we determined that culture time can serve as a proxy of the maturity level of hPSC-CMs. Second, we selected key heart-related genes whose expression varies with culture time, based on machine learning algorithms that are applied to accurately predict culture time. Our results demonstrate that the average discrepancy between the predicted culture time and the observed culture time can be reduced to 4.461 days. Furthermore, Gene CASQ2 (Calsequestrin 2), whose protein plays a role in the storage and transportation of calcium ions, has been identified as the most important cardiac gene that correlates with the culture duration.