Sca-1 Knockout Impairs Myocardial and Cardiac Progenitor Cell Function

RATIONALE:Cardiac progenitor cells are important for maintenance of myocardial structure and function, but molecular mechanisms governing these progenitor cells remain obscure and require elucidation to enhance regenerative therapeutic approaches. OBJECTIVE:To understand consequences of stem cell an...

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Published in:	Circulation research Vol. 111; no. 6; pp. 750 - 760
Main Authors:	Bailey, Brandi, Fransioli, Jenna, Gude, Natalie A, Alvarez, Roberto, Zhan, Xiaoxue, Gustafsson, Åsa B, Sussman, Mark A
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD American Heart Association, Inc 31-08-2012 Lippincott Williams & Wilkins
Subjects:	Animals Antigens, Ly - genetics Antigens, Ly - metabolism beta Catenin - genetics beta Catenin - metabolism Biological and medical sciences Cell Proliferation Cells, Cultured Echocardiography Female Fundamental and applied biological sciences. Psychology Gene Expression Profiling Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Heart - physiopathology Hypertrophy Male Membrane Proteins - genetics Membrane Proteins - metabolism Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Microscopy, Confocal Myocardial Contraction - genetics Myocardial Contraction - physiology Myocardium - metabolism Myocardium - pathology Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Proto-Oncogene Proteins c-kit - genetics Proto-Oncogene Proteins c-kit - metabolism Reverse Transcriptase Polymerase Chain Reaction Stem Cells - metabolism Stem Cells - pathology Time Factors Vertebrates: cardiovascular system Wnt Signaling Pathway - genetics Wnt Signaling Pathway - physiology Heart Cell function Infarct c-kit Precursor cell infarction cardiac progenitor cell β-catenin Vertebrata Mammalia Sca-1 β Catenin Development Myocardium Circulatory system Mutation cardiac development Progenitor cell Sca-1 knock-out
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Summary:	RATIONALE:Cardiac progenitor cells are important for maintenance of myocardial structure and function, but molecular mechanisms governing these progenitor cells remain obscure and require elucidation to enhance regenerative therapeutic approaches. OBJECTIVE:To understand consequences of stem cell antigen-1 (Sca-1) deletion on functional properties of c-kit+ cardiac progenitor cells and myocardial performance using a Sca-1 knock-out/green fluorescent protein knock-in reporter mouse (ScaKI). METHODS AND RESULTS:Genetic deletion of Sca-1 results in early-onset cardiac contractile deficiency as determined by echocardiography and hemodynamics as well as age-associated hypertrophy. Resident cardiac progenitor cells in ScaKI mice do not respond to pathological damage in vivo, consistent with observations of impaired growth and survival of ScaKI cardiac progenitor cells in vitro. The molecular basis of the defect in ScaKI cardiac progenitor cells is associated with increased canonical Wnt signaling pathway activation consistent with molecular characteristics of lineage commitment. CONCLUSIONS:Genetic deletion of Sca-1 causes primary cardiac defects in myocardial contractility and repair consistent with impairment of resident cardiac progenitor cell proliferative capacity associated with altered canonical Wnt signaling.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-7330 1524-4571
DOI:	10.1161/CIRCRESAHA.112.274662