c-kit+ cells minimally contribute cardiomyocytes to the heart

JH Van Berlo, O Kanisicak, M Maillet, RJ Vagnozzi… - Nature, 2014 - nature.com
JH Van Berlo, O Kanisicak, M Maillet, RJ Vagnozzi, J Karch, SCJ Lin, RC Middleton…
Nature, 2014nature.com
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 …
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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