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Genetic Lineage Tracing of Sca-1+ Cells Reveals Endothelial but Not Myogenic Contribution to the Murine Heart

Ronald J Vagnozzi1, Michelle A Sargent1, Suh-Chin J Lin1

  • 1Department of Pediatrics (R.J.V., M.A.S., S.-C.J.L., J.D.M.), Cincinnati Children's Hospital Medical Center, OH.

Circulation
|July 12, 2018
PubMed

Insights

Cardiac stem cells expressing Sca-1 (stem cell antigen-1) do not significantly contribute to new cardiomyocyte formation. Instead, Sca-1 positive cells are vascular endothelial cells that expand after injury, aiding heart repair.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Research
  • Regenerative Medicine

Background:

  • The adult mammalian heart has a low cardiomyocyte turnover rate (≈1%/year) postnatally and after myocardial infarction (MI).
  • Cardiac-resident stem cells, identified by stem cell antigen-1 (Sca-1), have been proposed as a source for cardiomyocyte renewal.
  • The in vivo contribution of endogenous Sca-1+ cells to cardiomyocyte regeneration after MI remains uninvestigated.

Purpose of the Study:

  • To investigate the in vivo contribution of endogenous Sca-1+ cells to cardiomyocyte renewal and cardiac vasculature.
  • To determine the role of Sca-1+ cells in cardiac development, aging, and response to myocardial infarction.

Main Methods:

  • Generation of Ly6a gene-targeted mice with constitutive or inducible Cre recombinase for lineage tracing.
  • Genetic lineage tracing of Sca-1+ cells in vivo at baseline and after myocardial infarction.
  • Pulse labeling of Sca-1+ cells using an inducible Ly6a-MerCreMer allele.

Main Results:

  • Endogenous Sca-1+ cells contributed <0.005% to the cardiomyocyte population throughout cardiac development, aging, and post-MI.
  • Sca-1+ cells significantly contributed to the cardiac vasculature during physiological growth and post-MI remodeling.
  • Lineage tracing revealed postnatal expansion of Sca-1+ endothelial cells and their preferential expansion after MI injury.

Conclusions:

  • Cardiac-resident Sca-1+ cells are not a significant source of cardiomyocyte renewal in vivo.
  • Cardiac Sca-1+ cells represent a subset of vascular endothelial cells that expand postnatally.
  • These Sca-1+ vascular endothelial cells exhibit enhanced responsiveness to pathological stress, contributing to cardiac repair mechanisms.
Abstract

Keywords:
cell lineageendothelial cellsmyocardial infarctionregenerationstem cells

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