BRIEF RESEARCH REPORT article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
This article is part of the Research TopicBioengineering and Biotechnology Approaches in Cardiovascular Sciences, Volume IIIView all 6 articles
Transcriptome-based Maturation Assessment Revealed Pro-maturation Transcription Factors of Cardiomyocytes
Provisionally accepted
Nawin Chanthra1,2
Sean Murphy3
Matthew Miyamoto3Nanami Masuyama4Nozomu Yachie4,5Chulan Kwon3
Hideki Uosaki1,6*- 1Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan
- 2Department of Biochemistry and Genetic Engineering, Faculty of Medicine, Kasetsart University, Bangkok, Thailand
- 3Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, United States
- 4School of Biomedical Engineering, Faculty of Applied Science and Faculty of Medicine, The University of British Columbia, Vancouver, Canada
- 5WPI Premium Research Institute for Human Metaverse Medicine, Osaka Daigaku, Suita, Japan
- 6Division of Functional Biochemistry, Department of Biochemistry, School of Medicine, Jichi Medical University, Shimotsuke, Japan
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Induced pluripotent stem cell-derived cardiomyocytes have shown promise to be an essential tool for studying genetic cardiac diseases. However, their limited maturity remains a barrier to reaching their full potential. Many have challenged this problem; however, it is difficult to compare the results because the parameters for cardiomyocyte maturation are diverse, mostly relying on physiological experiments that display significant lab-to-lab variations and are labor-intensive, and are not comparable to maturing cardiomyocytes in vivo. Here, we propose a transcriptome-based scoring method for cardiomyocyte maturation. We first established the maturation score based on transcriptome of mouse ventricles from embryonic (day 11) to adult (10-month-old) ventricles. We then demonstrated that known maturation conditions increased the maturation scores of mouse embryonic stem cell-derived cardiomyocytes. We finally performed expression screening of 92 candidate transcriptional factors (TFs) and identified pro-maturation TFs, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), PGC1β, and estrogen-related receptor alpha (ERRα). These results support that the transcriptome-based maturation score is a quantitative and reliable approach for identifying pro-maturation factors for cardiomyocytes.
Keywords: cardiomyocytes, ERRα, maturation, PGC1, Pluripotent Stem Cells, transcriptional factors
Received: 03 Oct 2025; Accepted: 23 Jan 2026.
Copyright: © 2026 Chanthra, Murphy, Miyamoto, Masuyama, Yachie, Kwon and Uosaki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hideki Uosaki
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