Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies.

Cell Reports
Rebecca WindmuellerEdward E Morrisey

Abstract

The mammalian heart is incapable of regenerating a sufficient number of cardiomyocytes to ameliorate the loss of contractile muscle after acute myocardial injury. Several reports have demonstrated that mononucleated cardiomyocytes are more responsive than are binucleated cardiomyocytes to pro-proliferative stimuli. We have developed a strategy to isolate and characterize highly enriched populations of mononucleated and binucleated cardiomyocytes at various times of development. Our results suggest that an E2f/Rb transcriptional network is central to the divergence of these two populations and that remnants of the differences acquired during the neonatal period remain in adult cardiomyocytes. Moreover, inducing binucleation by genetically blocking the ability of cardiomyocytes to complete cytokinesis leads to a reduction in E2f target gene expression, directly linking the E2f pathway with nucleation. These data identify key molecular differences between mononucleated and binucleated mammalian cardiomyocytes that can be used to leverage cardiomyocyte proliferation for promoting injury repair in the heart.

Citations

Nov 5, 2020·Journal of Cellular and Molecular Medicine·Haotong LiShengshou Hu
May 6, 2021·Cellular and Molecular Life Sciences : CMLS·Phong D NguyenJeroen Bakkers
Mar 2, 2021·Cell Regeneration·Stephen Cutie, Guo N Huang
Jul 1, 2021·Cold Spring Harbor Perspectives in Biology·Hui-Min YinCaroline E Burns

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Datasets Mentioned

BETA
GSE140851

Methods Mentioned

BETA
fluorescence-activated cell sorting
FACS
RNA-seq
transmission electron microscopy
Transgenic
dissection
PCR
PCA
Digestion

Software Mentioned

GSEA
Picard
R package
FastQC
AMT Advantage
ToppGene Suite
STAR aligner
FACS
MATLAB
MIQuant

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