The number one cause of death in the US and developed world is heart failure consequent to infarct. Primary goals for cardiac repair are to replace cardiomyocytes, stabilize neovascularization, and prevent scar formation. In contrast to mammalian myocardium, zebrafish heart regenerates post-injury by myocyte replacement, neoangiogenesis, and resolution of scar tissue. Regeneration of zebrafish heart requires activation of cells which outline the heart, the epicardium, but how epicardium contributes to regeneration is not known. During mouse heart development, epicardium gives rise to a number of cell types, including vascular support cells and cardiomyocytes. Although these data suggest the potential of epicardium to contribute cells for cardiac repair, adult epicardial cells lose the ability to become cardiomyocytes. Epicardial lineages also give rise to cardiac fibroblasts/myofibroblasts, which contribute to scarring post-infarct. Hepatic stellate cells (HSCs) share an embryonic origin with epicardial fibroblasts, and also contribute to fibrosis following acute liver injury. However, HSCs undergo senescence to promote scar resolution during liver regeneration. These findings suggest our goal, which is to achieve cardiac regeneration by promoting epicardial cells to adopt cardiomyocyte cell fates post-injury, and cardiac fibroblasts to undergo senescence to resolve scar formation. Toward this goal, we will generate new models of cardiac injury and new approaches for epicardial fate mapping to examine epicardial behavior post-injury in developing and adult mouse heart. We will identify mechanisms underlying the ability of embryonic epicardial cells to adopt cardiomyocyte cell fates, and apply this knowledge to promote adult epicardial cells becoming cardiomyocytes post-injury. We will gain insights into senescence behavior of cardiac fibroblasts, to activate these pathways in an injury setting. If successful, results of these studies will define new therapeuti

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
NIH Director’s Pioneer Award (NDPA) (DP1)
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Special Emphasis Panel (ZGM1-NDPA-B (02))
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Adhikari, Bishow B
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University of California San Diego
Schools of Pharmacy
La Jolla
United States
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Hirai, Maretoshi; Cattaneo, Paola; Chen, Ju et al. (2016) Revisiting Preadolescent Cardiomyocyte Proliferation in Mice. Circ Res 118:916-9
Moore-Morris, Thomas; Cattaneo, Paola; Puceat, Michel et al. (2016) Origins of cardiac fibroblasts. J Mol Cell Cardiol 91:1-5
Bolt, C Chase; Negi, Soumya; Guimarães-Camboa, Nuno et al. (2016) Tbx18 Regulates the Differentiation of Periductal Smooth Muscle Stroma and the Maintenance of Epithelial Integrity in the Prostate. PLoS One 11:e0154413
Boogerd, Cornelis J; Aneas, Ivy; Sakabe, Noboru et al. (2016) Probing chromatin landscape reveals roles of endocardial TBX20 in septation. J Clin Invest 126:3023-35
Liang, Xingqun; Zhang, Qingquan; Cattaneo, Paola et al. (2015) Transcription factor ISL1 is essential for pacemaker development and function. J Clin Invest 125:3256-68
Sinha, Tanvi; Lin, Lizhu; Li, Ding et al. (2015) Mapping the dynamic expression of Wnt11 and the lineage contribution of Wnt11-expressing cells during early mouse development. Dev Biol 398:177-92
Guimarães-Camboa, Nuno; Stowe, Jennifer; Aneas, Ivy et al. (2015) HIF1α Represses Cell Stress Pathways to Allow Proliferation of Hypoxic Fetal Cardiomyocytes. Dev Cell 33:507-21
Moore-Morris, Thomas; Guimarães-Camboa, Nuno; Yutzey, Katherine E et al. (2015) Cardiac fibroblasts: from development to heart failure. J Mol Med (Berl) 93:823-30
Moore-Morris, Thomas; Guimarães-Camboa, Nuno; Banerjee, Indroneal et al. (2014) Resident fibroblast lineages mediate pressure overload-induced cardiac fibrosis. J Clin Invest 124:2921-34
Moore-Morris, Thomas; Tallquist, Michelle D; Evans, Sylvia M (2014) Sorting out where fibroblasts come from. Circ Res 115:602-4

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