High-Throughput Screening Assay for the Identification of Compounds Regulating Self-Renewal and Differentiation in Human Embryonic Stem Cells Journal Article

   

Authors:	Desbordes, S. C.; Placantonakis, D. G.; Ciro, A.; Socci, N. D.; Lee, G.; Djaballah, H.; Studer, L.
Article Title:	High-Throughput Screening Assay for the Identification of Compounds Regulating Self-Renewal and Differentiation in Human Embryonic Stem Cells
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. © 2008 Elsevier Inc. All rights reserved.
Keywords:	controlled study; protein expression; antibiotic agent; human cell; nonhuman; research design; animal cell; mouse; cytology; animals; mice; cell structure; gene expression profiling; cell growth; embryo; embryonic stem cell; cell fate; cell renewal; cell differentiation; cardiac glycoside; drug structure; high throughput screening; dose-response relationship, drug; drug evaluation, preclinical; small molecule libraries; drug design; cell lineage; regeneration; fibroblast growth factor 2; drug research; cell culture; immunocytochemistry; microarray analysis; stemcell; embryonic stem cells; hoe 33342; cell nucleus; pluripotent stem cell; bone morphogenetic protein 2; biological assay; cell separation; retinoic acid; octamer transcription factor 4; embryo research; confocal laser microscopy; somatomedin b; transcription factor nanog; antiinflammatory agent; transcription factor sox17; bone morphogenetic protein 4; cell manipulation; 2 (2 amino 3 methoxyphenyl)chromone; cymarin; flurbiprofen; gatifloxacin; selegiline; sinomenine
Journal Title:	Cell Stem Cell
Volume:	2
Issue:	6
ISSN:	1934-5909
Publisher:	Cell Press
Date Published:	2008-06-05
Start Page:	602
End Page:	612
Language:	English
DOI:	10.1016/j.stem.2008.05.010
PUBMED:	18522853
PROVIDER:	scopus
PMCID:	PMC2756729
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-44349152907&partnerID=40&md5=16bea6da127474a46d1cdb63010bca10
Notes:	--- - "Cited By (since 1996): 57" - "Export Date: 17 November 2011" - "Source: Scopus"

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