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Updated: Feb 4, 2026

Maturation of Human Stem Cell-derived Cardiomyocytes in Biowires Using Electrical Stimulation
Published on: May 6, 2017
Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs Reveals HOPX-Dependent Cardiomyocyte
Clayton E Friedman1, Quan Nguyen2, Samuel W Lukowski2
1Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; Centre for Cardiac and Vascular Biology, The University of Queensland, Brisbane, QLD 4072, Australia.
Abstract:
Cardiac differentiation of human pluripotent stem cells (hPSCs) requires orchestration of dynamic gene regulatory networks during stepwise fate transitions but often generates immature cell types that do not fully recapitulate properties of their adult counterparts, suggesting incomplete activation of key transcriptional networks. We performed extensive single-cell transcriptomic analyses to map fate choices and gene expression programs during cardiac differentiation of hPSCs and identified strategies to improve in vitro cardiomyocyte differentiation. Utilizing genetic gain- and loss-of-function approaches, we found that hypertrophic signaling is not effectively activated during monolayer-based cardiac differentiation, thereby preventing expression of HOPX and its activation of downstream genes that govern late stages of cardiomyocyte maturation. This study therefore provides a key transcriptional roadmap of in vitro cardiac differentiation at single-cell resolution, revealing fundamental mechanisms underlying heart development and differentiation of hPSC-derived cardiomyocytes.
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