Systematic selection of small molecules to promote differentiation of embryonic stem cells and experimental validation for generating cardiomyocytes
Authors
KalantarMotamedi, Yasaman
Peymani, Maryam
Baharvand, Hossein
Nasr-Esfahani, Mohammad Hossein
Publication Date
2016-02-08Journal Title
Cell Death Discovery
ISSN
2058-7716
Publisher
Nature Publishing Group
Volume
2
Number
16007
Language
English
Type
Article
Metadata
Show full item recordCitation
KalantarMotamedi, Y., Peymani, M., Baharvand, H., Nasr-Esfahani, M. H., & Bender, A. (2016). Systematic selection of small molecules to promote differentiation of embryonic stem cells and experimental validation for generating cardiomyocytes. Cell Death Discovery, 2 (16007)https://doi.org/10.1038/cddiscovery.2016.7
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.
Sponsorship
YK and AB thank the European Research Council (ERC Starting Grant 2013 to AB) for funding.
Funder references
European Research Council (336159)
Embargo Lift Date
2300-01-01
Identifiers
External DOI: https://doi.org/10.1038/cddiscovery.2016.7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253248
Rights
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/