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First published online March 22, 2007
Stem Cells Vol. 25 No. 6 June 2007, pp. 1539 -1545
doi:10.1634/stemcells.2006-0485; www.StemCells.com
© 2007 AlphaMed Press

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EMBRYONIC STEM CELLS: CHARACTERIZATION SERIES

High-Throughput Identification of Genes Promoting Neuron Formation and Lineage Choice in Mouse Embryonic Stem Cells

Anna Falk, Tobias E. Karlsson, Sanja Kurdija, Jonas Frisén, Joel Zupicich

Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden

Key Words. Developmental biology • Gene expression • Fluorescence-activated cell sorting analysis • Embryonic stem cells • Fluorescent protein reporter genes • Gene delivery systems in vivo or in vitro • Stem cell culture • Neural differentiation

Correspondence: Jonas Frisén, M.D., Ph.D., Karolinska Institute, Cell and Developmental Biology, Box 285, Stockholm 17177, Sweden. Telephone: +46-8-52487562; Fax: +46-8-324927; e-mail: jonas.frisen{at}ki.se

Received August 1, 2006; accepted for publication March 12, 2007.
First published online in STEM CELLS EXPRESS   March 22, 2007.



The potential of embryonic stem cells to differentiate to all cell types makes them an attractive model for development and a potential source of cells for transplantation therapies. Candidate approaches have identified individual genes and proteins that promote the differentiation of embryonic stem cells to desired fates. Here, we describe a rapid large-scale screening strategy for the identification of genes that influence the pluripotency and differentiation of embryonic stem cells to specific fates, and we use this approach to identify genes that induce neuron formation. The power of the strategy is validated by the fact that, of the 15 genes that resulted in the largest increase in neuron number, 8 have previously been implicated in neuronal differentiation or survival, whereas 7 represent novel genes or known genes not previously implicated in neuronal development. This is a simple, fast, and generally applicable strategy for the identification of genes promoting the formation of any specific cell type from embryonic stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.




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