Abstract
Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.
Original language | English (US) |
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Pages (from-to) | 571-582 |
Number of pages | 12 |
Journal | Cell Reports |
Volume | 18 |
Issue number | 2 |
DOIs | |
State | Published - Jan 10 2017 |
Keywords
- ARVC
- T-tubule
- calcium transient
- cardiac progenitor
- cardiomyocyte
- cardiomyopathy
- disease modeling
- iPS
- maturation
- neonatal
- sarcomere shortening
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology