Single-cell RNA sequencing reveals maturation trajectory in human pluripotent stem cell-derived cardiomyocytes in engineered tissues

• Published in: iScience Vol. 26; no. 4; p. 106302
• Main Authors: Cheng, Shangli, Brenière-Letuffe, David, Ahola, Virpi, Wong, Andy O.T., Keung, Hoi Yee, Gurung, Bimal, Zheng, Zongli, Costa, Kevin D., Lieu, Deborah K., Keung, Wendy, Li, Ronald A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.04.2023; Elsevier
• Subjects: Cell biology; Stem cells research; Tissue Engineering; Cell biology; Stem cells research; Tissue Engineering
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106302

Cardiac in vitro models have become increasingly obtainable and affordable with the optimization of human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) differentiation. However, these CMs are immature compared to their in vivo counterparts. Here we study the cellular phenotype of hPSC-CMs by comparing their single-cell gene expression and functional profiles in three engineered cardiac tissue configurations: human ventricular (hv) cardiac anisotropic sheet, cardiac tissue strip, and cardiac organoid chamber (hvCOC), with spontaneously aggregated 3D cardiac spheroids (CS) as control. The CM maturity was found to increase with increasing levels of complexity of the engineered tissues from CS to hvCOC. The contractile components are the first function to mature, followed by electrophysiology and oxidative metabolism. Notably, the 2D tissue constructs show a higher cellular organization whereas metabolic maturity preferentially increases in the 3D constructs. We conclude that the tissue engineering models resembling configurations of native tissues may be reliable for drug screening or disease modeling. [Display omitted] •scRNA-seq allows accurate evaluation of maturation of engineered cardiac tissues•Unique microenvironment in engineered cardiac tissues promote maturation•CM maturity increases with increasing levels of complexity of the engineered tissues Cell biology; Stem cells research; Tissue Engineering