Abstract
A phenotypic cell-based screen of a large combinatorial chemical library led to the identification of a class of diaminopyrimidine compounds (cardiogenol A-D) which can selectively and efficiently induce mouse embryonic stem cells (ESCs) to differentiate into cardiomyocytes. ESC-derived cardiomyocytes were shown to express multiple cardiac muscle markers, including myosin heavy chain, GATA-4, MEF2, and Nkx2.5, and spontaneously form beating regions. Such small molecules will serve as useful chemical probes to study cardiac muscle differentiation and may ultimately facilitate the therapeutic application of ESCs for cardiac repair.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aniline Compounds / pharmacology
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Animals
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Atrial Natriuretic Factor / genetics
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Cell Differentiation / drug effects
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Cell Line, Tumor
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DNA-Binding Proteins / biosynthesis
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GATA4 Transcription Factor
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Genetic Markers
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Mice
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Myocytes, Cardiac / cytology*
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Myocytes, Cardiac / drug effects*
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Myocytes, Cardiac / metabolism
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Myosin Heavy Chains / biosynthesis
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Pluripotent Stem Cells / cytology*
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Pluripotent Stem Cells / drug effects*
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Pluripotent Stem Cells / metabolism
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Promoter Regions, Genetic
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Pyrimidines / pharmacology
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Rats
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Transcription Factors / biosynthesis
Substances
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Aniline Compounds
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DNA-Binding Proteins
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GATA4 Transcription Factor
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Gata4 protein, mouse
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Gata4 protein, rat
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Genetic Markers
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Pyrimidines
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Transcription Factors
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cardiogenol C
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Atrial Natriuretic Factor
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Myosin Heavy Chains