A recessive genetic screens to identify regulators of embryonic stem cell self-renewal and lineage commitment

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Embryonic stem (ES) cells exhibit indefinite growth in culture while retaining the potential to differentiate into all fetal or adult cell types. The application of ES cells in regenerative medicine requires that ES cell differentiation in culture be directed to become a specific cell type, such as dopaminergic nerve cells, which could be used to replace the damaged nerves in Parkinson‘s disease patients. However, at present we are unable to reliably direct cell differentiation in this way, so even when we successfully generate nerve cells they tend to be mixed together with other unwanted types. Better understanding of the genes and molecular signaling involved in ES cell growth and differentiation in culture will help develop new culture systems for directed ES cell differentiation. Application of new techniques, such as the proposed recessive genetic screen, to the study of ES cell biology and in vitro differentiation will allow us to find novel components as well as bring new views to the established ES cell regulatory pathways.