Abstract 17713: Abcg2 Regulates Asymmetric Cell Division In Mouse Cardiac Progenitor Cells
Recently, the identification of adult resident cardiac progenitor cell populations and their potential to regenerate cardiac tissue has provided a therapeutic alternative for the treatment of heart failure. The mechanisms regulating cardiac progenitor cell self-renewal and differentiation, however, remain unknown. Progenitor cell homeostasis is controlled through a balance between symmetric and asymmetric cell kinetics. Several lines of evidence have associated cell cycle length with asymmetric division. We have previously shown that the ABC transporter Abcg2 promotes cardiac side population (CSP) progenitor cell proliferation and survival. We therefore examined the hypothesis that Abcg2 affects CSP cell proliferation through regulation of cell cycle progression and asymmetric cell kinetics.
Methods and Results: The cell cycle profile of WT and Abcg2-deficient CSP cells was studied using the lentiviral-based fluorescence ubiquitination cell cycle indicator (FUCCI) system in combination with live cell confocal microscopy and RT-PCR arrays. We found that Abcg2-deficient CSP cells exhibit prolonged cell cycle duration and delayed G1-S transition. Moreover, genes related to cell cycle progression were down-regulated and cell cycle inhibitory genes were activated in Abcg2-deficient CSP cells. Interestingly, DNA damage response was also activated as evidenced by both RT-PCR for DNA damage related genes and immuno-cytochemical staining for phospho-H2AX. Importantly, CSP cells lacking Abcg2 demonstrated higher levels of asymmetrically dividing cells compared to WT.
In conclusion, our work reveals for the first time a role for Abcg2 in cardiac progenitor cell cycle progression and division mode and further supports the notion that cell cycle length is linked to asymmetric cell kinetics. Manipulation of Abcg2 activity may provide a new therapeutic approach for stimulation of cardiac progenitor cells and cardiac regeneration.
- © 2012 by American Heart Association, Inc.