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

被引：170

作者：

Desbordes, Sabrina C. ^{[1
,5
]}

Placantonakis, Dimitris G. ^{[1
,4
]}

Ciro, Anthony ^{[2
]}

Socci, Nicholas D. ^{[3
]}

Lee, Gabsang ^{[1
,5
]}

Djaballah, Hakim ^{[2
]}

Studer, Lorenz ^{[1
,5
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, High Throughput Screening Core Facil, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10021 USA

[4] Weill Cornell Med Coll, Dept Neurol Surg, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10021 USA

来源：

CELL STEM CELL | 2008年 / 2卷 / 06期

关键词：

D O I：

10.1016/j.stem.2008.05.010

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：602 / 612

页数：11

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