Analysis of cardiomyocyte clonal expansion during mouse heart development and injury

Nature Communications
Konstantina-Ioanna SeretiReza Ardehali

Abstract

The cellular mechanisms driving cardiac tissue formation remain poorly understood, largely due to the structural and functional complexity of the heart. It is unclear whether newly generated myocytes originate from cardiac stem/progenitor cells or from pre-existing cardiomyocytes that re-enter the cell cycle. Here, we identify the source of new cardiomyocytes during mouse development and after injury. Our findings suggest that cardiac progenitors maintain proliferative potential and are the main source of cardiomyocytes during development; however, the onset of αMHC expression leads to reduced cycling capacity. Single-cell RNA sequencing reveals a proliferative, "progenitor-like" population abundant in early embryonic stages that decreases to minimal levels postnatally. Furthermore, cardiac injury by ligation of the left anterior descending artery was found to activate cardiomyocyte proliferation in neonatal but not adult mice. Our data suggest that clonal dominance of differentiating progenitors mediates cardiac development, while a distinct subpopulation of cardiomyocytes may have the potential for limited proliferation during late embryonic development and shortly after birth.

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Citations

Jun 9, 2018·Genes·Michal PawlakCecilia Lanny Winata
Jul 20, 2019·Journal of the American Heart Association·Yang LiuDeyou Zheng
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Apr 7, 2021·Cell Regeneration·Lixia ZhengJing-Wei Xiong

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Datasets Mentioned

BETA
GSE10842

Methods Mentioned

BETA
transgenic
fluorescence microscopy
chip
genotyping
PCR
dissection
FACS
RNASeq

Software Mentioned

ggplot2
pheatmap
STRING ( Search Tool for the Retrieval of Interacting Genes Pr...
Rainbow
featurecCounts
Metascape
OLego
StepMiner
R scripts
Fluidigm

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