Abstract 14917: Cardiac Lineage Tracing Analysis at Baseline and With Injury Using Inducible C-kit-cre Knockin Mice
Introduction: In the last decade a number of different cell sources have been implicated in contributing to the myocardium after injury to regenerate this organ. One of the most highly studied has been c-kit positive cardiac progenitor cells (CPCs) that take up residence in the heart where they subsequently contribute differentiated lineages to help regenerate the heart (cardiomyocytes, endothelial and smooth cells). However, the extent to which this process occurs in vivo has been a source of great debate.
Methods: We generated a mouse model in which a cDNA cassette expressing the tamoxifen inducible MerCreMer protein was “knocked” into the endogenous c-kit locus. The mice were cross-bred to reporter mice containing a conditional eGFP expression locus that upon Cre recombinase activation in any tissue, marked cells irrevocably. We performed long-term lineage tracing in the heart as well as after myocardial infarction. Analysis of bone marrow and testis demonstrated abundant labeling with the c-kit-MerCreMer approach, demonstrating the fidelity and robustness of the approach and the knockin allele.
Results: and Discussion We provided tamoxifen to label any c-kit lineage cells that might be contributing to the heart from 0-6 months of age, as well as from 2-9 months of age. We also labeled cells from 0-4 weeks of age to more specifically address the contribution of c-kit lineage cells to the heart during postnatal development. Finally, we also provided tamoxifen to adult mice for 2 and 4 weeks after myocardial infarction injury to quantify production of new myocytes (and other cell types as well) from the c-kit lineage. The results support the general notion that c-kit cells can contribute to the myocardium but a discussion of the quantities and types of cells will be presented.
- © 2013 by American Heart Association, Inc.