title: Notch signaling respecifies the hemangioblast to a cardiac fate.
abstract: To efficiently generate cardiomyocytes from embryonic stem (ES) cells in culture it is essential to identify key regulators of the cardiac lineage and to develop methods to control them. Using a tet-inducible mouse ES cell line to enforce expression of a constitutively activated form of the Notch 4 receptor, we show that signaling through the Notch pathway can efficiently respecify hemangioblasts to a cardiac fate, resulting in the generation of populations consisting of >60% cardiomyocytes. Microarray analyses reveal that this respecification is mediated in part through the coordinated regulation of the BMP and Wnt pathways by Notch signaling. Together, these findings have uncovered a potential role for the Notch pathway in cardiac development and provide an approach for generating large numbers of cardiac progenitors from ES cells.
authors.affiliation: Department of Gene and Cell Medicine, The Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Chen
authors.forename: Robert
authors.initials: R
authors.lastname: Stull
authors.forename: Daniel
authors.initials: D
authors.lastname: Joo
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Gordon
authors.initials: G
authors.lastname: Keller
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D055018:Hemangioblasts / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch