TY - JOUR T1 - <em>Abcg2</em>-Expressing Side Population Cells Contribute to Cardiomyocyte Renewal through Fusion JF - bioRxiv DO - 10.1101/690339 SP - 690339 AU - Amritha Yellamilli AU - Yi Ren AU - Ron T. McElmurry AU - Jonathan P. Lambert AU - Polina Gross AU - Sadia Mohsin AU - Steven R. Houser AU - John W. Elrod AU - Jakub Tolar AU - Daniel J. Garry AU - Jop H. van Berlo Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/02/690339.abstract N2 - The adult mammalian heart has a limited regenerative capacity. Therefore, identification of endogenous cells and mechanisms that contribute to cardiac regeneration is essential for the development of targeted regenerative therapies. The side population (SP) phenotype enriches for stem cells throughout the body, and SP cells have been identified in the heart. We generated a novel Abcg2-driven, genetic lineage-tracing mouse model and show efficient labeling of SP cells. Labeled SP cells give rise to terminally differentiated cells in bone marrow and intestines. In the heart, we find that Abcg2-expressing SP cells contribute to cardiomyocyte labeling, which is further enhanced in response to different forms of cardiac injury. We find that cardiac SP cells fuse with preexisting cardiomyocytes, which stimulates cardiomyocyte cell cycle entry and likely proliferation, instead of directly differentiating into cardiomyocytes. Our findings provide evidence that cardiac SP cells contribute to endogenous cardiac regeneration through cardiomyocyte fusion. ER -