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Systematic selection of small molecules to promote differentiation of embryonic stem cells and experimental validation for generating cardiomyocytes.

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KalantarMotamedi, Y 
Peymani, M 
Baharvand, H 
Nasr-Esfahani, MH 


Small molecules are being increasingly used for inducing the targeted differentiation of stem cells to different cell types. However, until now no systematic method for selecting suitable small molecules for this purpose has been presented. In this work, we propose an integrated and general bioinformatics- and cheminformatics-based approach for selecting small molecules which direct cellular differentiation in the desired way. The approach was successfully experimentally validated for differentiating stem cells into cardiomyocytes. All predicted compounds enhanced expression of cardiac progenitor (Gata4, Nkx2-5 and Mef2c) and mature cardiac markers (Actc1, myh6) significantly during and post-cardiac progenitor formation. The best-performing compound, Famotidine, increased the percentage of Myh6-positive cells from 33 to 56%, and enhanced the expression of Nkx2.5 and Tnnt2 cardiac progenitor and cardiac markers in protein level. The approach employed in the study is applicable to all other stem cell differentiation settings where gene expression data are available.



0604 Genetics, 0601 Biochemistry and Cell Biology, Biomedical, Basic Science, Cardiovascular, Stem Cell Research, Stem Cell Research - Embryonic - Non-Human, Heart Disease, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Cardiovascular, 5.2 Cellular and gene therapies

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Cell Death Discov

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Springer Science and Business Media LLC
European Research Council (336159)
YK and AB thank the European Research Council (ERC Starting Grant 2013 to AB) for funding.