High-throughput identification of genes promoting neuron formation and lineage choice in mouse embryonic stem cells

¹ Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden

^* To whom correspondence should be addressed. E-mail: jonas.frisen{at}ki.se.

	Abstract

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, eight have previously been implicated in neuronal differentiation or survival, whereas seven 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.