期刊
CIRCULATION
卷 138, 期 25, 页码 2931-2939出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.118.035210
关键词
cell lineage; endothelial cells; myocardial infarction; regeneration; stem cells
资金
- National Institutes of Health
- Howard Hughes Medical Institute
- National Research Service Award from the National Institutes of Health [F32 HL128083]
BACKGROUND: The adult mammalian heart displays a cardiomyocyte turnover rate of approximate to 1%/y throughout postnatal life and after injuries such as myocardial infarction (MI), but the question of which cell types drive this low level of new cardiomyocyte formation remains contentious. Cardiac resident stem cells marked by stem cell antigen -1 (Sca-1, gene name Ly6a) have been proposed as an important source of cardiomyocyte renewal. However, the in vivo contribution of endogenous Sca-1(+) cells to the heart at baseline or after MI has not been investigated. METHODS: Here we generated Ly6a gene targeted mice containing either a constitutive or an inducible Cre recombinase to perform genetic lineage tracing of Sca-1(+) cells in vivo. RESULTS: We observed that the contribution of endogenous Sca-1(+) cells to the cardiomyocyte population in the heart was <0.005% throughout all of cardiac development, with aging, or after MI. In contrast, Sca-1(+) cells abundantly contributed to the cardiac vasculature in mice during physiological growth and in the post -MI heart during cardiac remodeling. Specifically, Sca-1 lineage -traced endothelial cells expanded postnatally in the mouse heart after birth and into adulthood. Moreover, pulse labeling of Sca-1(+) cells with an inducible Ly6a-MerCreMer allele also revealed a preferential expansion of Sca-1 lineage -traced endothelial cells after MI injury in the mouse. CONCLUSIONS: Cardiac -resident Sca-1 cells are not significant contributors to cardiomyocyte renewal in vivo. However, cardiac Sca1(+) cells represent a subset of vascular endothelial cells that expand postnatally with enhanced responsiveness to pathological stress in vivo.
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