High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells

• Published in: Cell stem cell Vol. 2; no. 6; pp. 602 - 612
• Main Authors: Desbordes, Sabrina C, Placantonakis, Dimitris G, Ciro, Anthony, Socci, Nicholas D, Lee, Gabsang, Djaballah, Hakim, Studer, Lorenz
• Format: Journal Article
• Language: English
• Published: United States 05.06.2008
• Subjects: Animals; Biological Assay; Cell Differentiation - drug effects; Dose-Response Relationship, Drug; Drug Design; Drug Evaluation, Preclinical; Embryo Research; Embryonic Stem Cells - cytology; Embryonic Stem Cells - drug effects; Humans; Mice; Microarray Analysis; Regeneration - drug effects; Research Design - trends; Small Molecule Libraries - pharmacology; Small Molecule Libraries - therapeutic use
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2008.05.010

High-throughput screening (HTS) of chemical libraries has become a critical tool in basic biology and drug discovery. However, its implementation and the adaptation of high-content assays to human embryonic stem cells (hESCs) have been hampered by multiple technical challenges. Here we present a strategy to adapt hESCs to HTS conditions, resulting in an assay suitable for the discovery of small molecules that drive hESC self-renewal or differentiation. Use of this new assay has led to the identification of several marketed drugs and natural compounds promoting short-term hESC maintenance and compounds directing early lineage choice during differentiation. Global gene expression analysis upon drug treatment defines known and novel pathways correlated to hESC self-renewal and differentiation. Our results demonstrate feasibility of hESC-based HTS and enhance the repertoire of chemical compounds for manipulating hESC fate. The availability of high-content assays should accelerate progress in basic and translational hESC biology.