NYMC Faculty Publications

In vitro CSC-Derived Cardiomyocytes Exhibit the Typical MicroRNA-mRNA Blueprint of Endogenous Cardiomyocytes

Author Type(s)

Faculty

DOI

10.1038/s42003-021-02677-y

Journal Title

Communications Biology

First Page

1146

Last Page

1146

Document Type

Article

Publication Date

9-30-2021

Department

Physiology

Keywords

Animals, Cell Cycle, Cell Differentiation, Mice, MicroRNAs, Muscle Development, Myocytes, Cardiac, RNA, Messenger, Stem Cells, Transcriptome, Up-Regulation

Disciplines

Medicine and Health Sciences

Abstract

miRNAs modulate cardiomyocyte specification by targeting mRNAs of cell cycle regulators and acting in cardiac muscle lineage gene regulatory loops. It is unknown if or to-what-extent these miRNA/mRNA networks are operative during cardiomyocyte differentiation of adult cardiac stem/progenitor cells (CSCs). Clonally-derived mouse CSCs differentiated into contracting cardiomyocytes in vitro (iCMs). Comparison of "CSCs vs. iCMs" mRNome and microRNome showed a balanced up-regulation of CM-related mRNAs together with a down-regulation of cell cycle and DNA replication mRNAs. The down-regulation of cell cycle genes and the up-regulation of the mature myofilament genes in iCMs reached intermediate levels between those of fetal and neonatal cardiomyocytes. Cardiomyo-miRs were up-regulated in iCMs. The specific networks of miRNA/mRNAs operative in iCMs closely resembled those of adult CMs (aCMs). miR-1 and miR-499 enhanced myogenic commitment toward terminal differentiation of iCMs. In conclusions, CSC specification/differentiation into contracting iCMs follows known cardiomyo-MiR-dependent developmental cardiomyocyte differentiation trajectories and iCMs transcriptome/miRNome resembles that of CMs.

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