Unknown

Dataset Information

0

Single-cell imaging and transcriptomic analyses of endogenous cardiomyocyte dedifferentiation and cycling.


ABSTRACT: While it is recognized that there are low levels of new cardiomyocyte (CM) formation throughout life, the source of these new CM generates much debate. One hypothesis is that these new CMs arise from the proliferation of existing CMs potentially after dedifferentiation although direct evidence for this is lacking. Here we explore the mechanisms responsible for CM renewal in vivo using multi-reporter transgenic mouse models featuring efficient adult CM (ACM) genetic cell fate mapping and real-time cardiomyocyte lineage and dedifferentiation reporting. Our results demonstrate that non-myocytes (e.g., cardiac progenitor cells) contribute negligibly to new ACM formation at baseline or after cardiac injury. In contrast, we found a significant increase in dedifferentiated, cycling CMs in post-infarct hearts. ACM cell cycling was enhanced within the dedifferentiated CM population. Single-nucleus transcriptomic analysis demonstrated that CMs identified with dedifferentiation reporters had significant down-regulation in gene networks for cardiac hypertrophy, contractile, and electrical function, with shifts in metabolic pathways, but up-regulation in signaling pathways and gene sets for active cell cycle, proliferation, and cell survival. The results demonstrate that dedifferentiation may be an important prerequisite for CM proliferation and explain the limited but measurable cardiac myogenesis seen after myocardial infarction (MI).

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6547664 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

altmetric image

Publications

Single-cell imaging and transcriptomic analyses of endogenous cardiomyocyte dedifferentiation and cycling.

Zhang Yiqiang Y   Gago-Lopez Nuria N   Li Ning N   Zhang Zhenhe Z   Alver Naima N   Liu Yonggang Y   Martinson Amy M AM   Mehri Avin A   MacLellan William Robb WR  

Cell discovery 20190604


While it is recognized that there are low levels of new cardiomyocyte (CM) formation throughout life, the source of these new CM generates much debate. One hypothesis is that these new CMs arise from the proliferation of existing CMs potentially after dedifferentiation although direct evidence for this is lacking. Here we explore the mechanisms responsible for CM renewal in vivo using multi-reporter transgenic mouse models featuring efficient adult CM (ACM) genetic cell fate mapping and real-tim  ...[more]

Similar Datasets

2019-07-02 | GSE129175 | GEO
| PRJNA530385 | ENA
| S-EPMC8448341 | biostudies-literature
| S-EPMC6172462 | biostudies-literature
| S-EPMC6684137 | biostudies-literature
| S-EPMC6220122 | biostudies-literature
| S-EPMC6677314 | biostudies-literature
2019-07-02 | GSE49448 | GEO
| S-EPMC7494622 | biostudies-literature
| S-EPMC2846535 | biostudies-literature