Key result
Endogenous Sca-1+ cells generate <0.005% of cardiomyocytes, instead forming vascular endothelial cells post-MI.
Why the study?
The in vivo contribution of endogenous Sca-1+ cells to cardiomyocyte renewal at baseline or after myocardial infarction had not been investigated.
Cardiac-resident Sca-1+ cells do not significantly contribute to cardiomyocyte renewal in vivo, but instead represent a subset of vascular endothelial cells that expand postnatally and after injury.
Answers are grounded in this paper and cite their sources.
Negligible Sca-1+ contribution to cardiomyocytes does not support their therapeutic targeting; challenges their proposed role as cardiac stem cells.
Background: The adult mammalian heart displays a cardiomyocyte turnover rate of ≈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 Sca-1 + cells represent a subset of vascular endothelial cells that expand postnatally with enhanced responsiveness to pathological stress in vivo.
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Vagnozzi et al. (2018) studied Myocardial infarction. Genetic lineage tracing of Sca-1+ cells was evaluated on Contribution of endogenous Sca-1+ cells to the cardiomyocyte population. Genetic lineage tracing in mice revealed that endogenous Sca-1+ cells contribute <0.005% to cardiomyocytes, instead expanding as vascular endothelial cells after myocardial infarction.
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