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

Shangli Cheng, David Brenière-Letuffe, Virpi Ahola, Andy O.T. Wong, Hoi Yee Keung, Bimal Gurung, Zongli Zheng, Kevin D. Costa, Deborah K. Lieu, Wendy Keung, Ronald A. Li

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Article number106302
JournaliScience
Volume26
Issue number4
DOIs
StatePublished - 21 Apr 2023

Keywords

  • Cell biology
  • Stem cells research
  • Tissue Engineering

Fingerprint

Dive into the research topics of 'Single-cell RNA sequencing reveals maturation trajectory in human pluripotent stem cell-derived cardiomyocytes in engineered tissues'. Together they form a unique fingerprint.

Cite this