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

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 str...

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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
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Abstract	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.
AbstractList	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.
Author	Socci, Nicholas D Lee, Gabsang Djaballah, Hakim Placantonakis, Dimitris G Desbordes, Sabrina C Studer, Lorenz Ciro, Anthony
AuthorAffiliation	5 Department of Neurological Surgery, Weill Cornell Medical College, 525 E68th Street, New York, NY 10021, USA 3 High Throughput Screening Core Facility, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10021, USA 2 Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10021, USA 1 Developmental Biology Program, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10021, USA 4 Computational Biology Center, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10021, USA
AuthorAffiliation_xml	– name: 5 Department of Neurological Surgery, Weill Cornell Medical College, 525 E68th Street, New York, NY 10021, USA – name: 1 Developmental Biology Program, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10021, USA – name: 3 High Throughput Screening Core Facility, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10021, USA – name: 4 Computational Biology Center, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10021, USA – name: 2 Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY, 10021, USA
Author_xml	– sequence: 1 givenname: Sabrina C surname: Desbordes fullname: Desbordes, Sabrina C email: sabrina.desbordes@crg.es organization: Developmental Biology Program, Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. sabrina.desbordes@crg.es – sequence: 2 givenname: Dimitris G surname: Placantonakis fullname: Placantonakis, Dimitris G – sequence: 3 givenname: Anthony surname: Ciro fullname: Ciro, Anthony – sequence: 4 givenname: Nicholas D surname: Socci fullname: Socci, Nicholas D – sequence: 5 givenname: Gabsang surname: Lee fullname: Lee, Gabsang – sequence: 6 givenname: Hakim surname: Djaballah fullname: Djaballah, Hakim – sequence: 7 givenname: Lorenz surname: Studer fullname: Studer, Lorenz
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: Differentiation and Cancer Program, Centre de Regulació Genòmica (CRG), C/ Dr. Aiguader 88, 08003 Barcelona, Spain
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Snippet	High-throughput screening (HTS) of chemical libraries has become a critical tool in basic biology and drug discovery. However, its implementation and the...
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SubjectTerms	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
Title	High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells
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