c-kitCre Knock-ins Fail to Identify, Effectively Recombine and Fate-Map Cardiac Stem Cells. Mus musculus

A recent cell-fate mapping study by Van Berlo et al. using a Cre knock-in (KI) into the c-kit locus, and two other studies using a similar genetic approach to track the fate of Cardiac Stem/progenitor Cells (CSCs) concluded that c-kitpos cells only negligibly generate cardiomyocytes. These papers questioned our findings that tissue-specific c-kitposCSCs are endogenous regenerative agents necessary and sufficient for cardiomyocyte regeneration/replenishment after injury. We consider answering whether the c-kitCre-KI approach properly identifies and fate-maps c-kitposCSCs and/or whether c-kitCre-KI-insertion affects CSC biology and cardiomyogenic potential. To test this hypothesis, we crossed the the c-kitCre-KI mouse to different reporter mouse models. We concluded that the c-kitCre-KI approach neither identifies nor fate-tracks the c-kitposCSCs, because c-kit expression level in these cells is too low to produce enough Cre to effectively recombine the floxed marker and permanently tag the CSC and their progeny. Overall design: RNA-seq data from CSCs, isolated from wt and c-kitCre mice (triplicated) have been analysed and compared.