title: Systematic selection of small molecules to promote differentiation of embryonic stem cells and experimental validation for generating cardiomyocytes.
abstract: 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.
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: KalantarMotamedi
authors.affiliation: Department of Cell and Molecular Biology, Cell Science Research Centre, Royan Institute for Biotechnology, ACECR , Isfahan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Peymani
authors.affiliation: Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Baharvand
authors.affiliation: Department of Cell and Molecular Biology, Cell Science Research Centre, Royan Institute for Biotechnology, ACECR , Isfahan, Iran.
authors.forename: M H
authors.initials: MH
authors.lastname: Nasr-Esfahani
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bender