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Abcg2 Regulates Cell Cycle Progression and Asymmetric Division in Mouse Cardiac Side Population Progenitor Cells.


Circ Res. 2012 Nov 6;


Authors: Sereti KI, Oikonomopoulos A, Unno K, Cao X, Qiu Y, Liao R


Abstract

Rationale: Following cardiac injury, cardiac progenitor cells are acutely reduced, and are replenished in part by regulated self-renewal and proliferation, which occurs through symmetric and asymmetric cellular division. Understanding the molecular cues controlling progenitor cell self-renewal and lineage commitment is critical towards harnessing these cells for therapeutic regeneration. We have previously found that the cell surface ATP binding cassette (ABC)-transporter, Abcg2, influences the proliferation of cardiac side population (CSP) progenitor cells, though through unclear mechanisms. Objective: To determine the role of Abcg2 on cell cycle progression and mode of division in mouse CSP cells. Methods and Results: Herein, using CSP cells isolated from wild-type and Abcg2-knockout mice, we find that Abcg2 regulates G1-S cell cycle transition by FUCCI cell cycle indicators, cell cycle-focused gene expression arrays and confocal live cell fluorescent microscopy. Moreover, we find that modulation of cell cycle results in transition from symmetric to asymmetric cellular division in CSP cells lacking Abcg2. Conclusions: Abcg2 modulates CSP cell cycle progression and asymmetric cell division, establishing a mechanistic link between this surface transporter and cardiac progenitor cell function. Greater understanding of progenitor cell biology, and in particular the regulation of resident progenitor cell homeostasis, is vital for guiding the future development of cell-based therapies for cardiac regeneration.

PMID: 23136123 [PubMed - as supplied by publisher]