Maturing heart muscle cells: Mechanisms and transcriptomic insights

Sean A Murphy; Elaine Zhelan Chen; Leslie Tung; Kenneth R Boheler; Chulan Kwon

doi:10.1016/j.semcdb.2021.04.019

Maturing heart muscle cells: Mechanisms and transcriptomic insights

Semin Cell Dev Biol. 2021 Nov:119:49-60. doi: 10.1016/j.semcdb.2021.04.019. Epub 2021 May 2.

Authors

Sean A Murphy¹, Elaine Zhelan Chen², Leslie Tung³, Kenneth R Boheler⁴, Chulan Kwon⁵

Affiliations

¹ Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: ltung@jhu.edu.
⁴ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: kbohele1@jhmi.edu.
⁵ Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: ckwon13@jhmi.edu.

Abstract

Cardiomyocyte (CM) maturation is the transformation of differentiated fetal CMs into adult CMs that involves changes in morphology, cell function and metabolism, and the transcriptome. This process is, however, incomplete and ultimately arrested in pluripotent stem cell-derived CMs (PSC-CMs) in culture, which hinders their broad biomedical application. For this reason, enormous efforts are currently being made with the goal of generating mature PSC-CMs. In this review, we summarize key aspects of maturation observed in native CMs and discuss recent findings on the factors and mechanisms that regulate the process. Particular emphasis is put on transcriptional regulation and single-cell RNA-sequencing analysis that has emerged as a key tool to study time-series gene regulation and to determine the maturation state. We then discuss different biomimetic strategies to enhance PSC-CM maturation and discuss their effects at the single cell transcriptomic and functional levels.

Keywords: Cardiomyocyte maturation; Heart development; Maturation metrics; Pluripotent stem cells; Single-cell transcriptomics; Tissue engineering.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Cell Differentiation
Humans
Myocytes, Cardiac / physiology*
Tissue Engineering / methods*
Transcriptome / physiology*

Abstract

Publication types

MeSH terms

Grants and funding