Sorensen, Daniel2022-06-082022-06-082022-03https://hdl.handle.net/11299/227931University of Minnesota Ph.D. dissertation. 2022. Major: Molecular, Cellular, Developmental Biology and Genetics. Advisors: Jop van Berlo, Yasuhiko Kawakami. 1 computer file (PDF); 127 pages.The mammalian heart loses almost all its regenerative potential in the first week of life due to the cessation of the ability of cardiomyocytes to proliferate. In recent years, a number of regulators of cardiomyocyte proliferation have been identified. Despite this, a clear understanding of the regulatory pathways that control cardiomyocyte proliferation and cardiac regeneration is lacking, and there are likely additional regulators to be discovered. Here, we performed a genome-wide screen on fetal murine cardiomyocytes to identify potential novel regulators of cardiomyocyte proliferation. Endoglin was identified as an inhibitor of cardiomyocyte proliferation in vitro. Endoglin knock-down resulted in enhanced DNA synthesis, cardiomyocyte mitosis and cytokinesis in mouse, rat and human cardiomyocytes. Using gene-targeted mice, we confirmed myocardial Endoglin to be important in cardiomyocyte proliferation and cardiac. Mechanistically, we show that Smad signaling is required for the endoglin-mediated anti-proliferative effects. Our results identify the TGF-β coreceptor Endoglin as a regulator of cardiac regeneration and cardiomyocyte proliferation.enCardiac RegenerationCardiomyocyteEndoglinTgf BetaThesis or Dissertation