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Induction of Endothelial Differentiation in Cardiac Progenitor Cells Under Low Serum Conditions
Published on: January 7, 2019
c-kit+ cells minimally contribute cardiomyocytes to the heart
Jop H van Berlo1, Onur Kanisicak2, Marjorie Maillet3
11] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Department of Medicine, division of Cardiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA [3].
Insights
Endogenous c-kit(+) cells can generate new cardiomyocytes in the heart, but at a very low, likely insignificant level. These cells also readily produce cardiac endothelial cells.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Regenerative Medicine
Background:
- The capacity of the heart to regenerate after injury is a critical question in cardiovascular research.
- c-kit-expressing cardiac progenitor cells are proposed as a key source for regenerating heart muscle (myocardium).
Purpose of the Study:
- To investigate the contribution of endogenous c-kit(+) cells to cardiomyocyte generation.
- To assess this contribution during heart development, aging, and after adult injury.
Main Methods:
- Generated two genetic mouse models targeting the Kit locus with Cre recombinase or MerCreMer.
- Utilized reporter lines for permanent lineage tracing of c-kit(+) cells.
- Examined cell differentiation into cardiomyocytes and cardiac endothelial cells.
Main Results:
- Endogenous c-kit(+) cells generated new cardiomyocytes at a very low percentage (≤0.03%, or <0.008% considering fusion).
- c-kit(+) cells were abundant in generating cardiac endothelial cells.
- Demonstrated that c-kit(+) cells can differentiate into cardiomyocytes in vivo.
Conclusions:
- Endogenous c-kit(+) cells contribute to cardiomyocyte generation in the heart, albeit at a functionally insignificant level.
- These progenitor cells are a significant source of cardiac endothelial cells.
- The role of c-kit(+) cells in cardiac regeneration may be limited to endothelial cell production.
Abstract:
If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.
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