Neural Differentiation of Embryonic Stem Cells

	[Enlarge Image] Neural Fate Specification of mouse ES cells.

The generation of unlimited numbers of dopamine neurons from mouse embryonic stem cells can be achieved in a multi-step differentiation protocol, allowing the sequential generation of embryonic stem cells, embryoid bodies, early ectodermal cells, proliferating CNS precursors, and differentiated neurons and glia. Alternatively, neural induction and directed differentiation into various neuronal and glial cell types can be achieved by co-culture with bone marrow-derived stromal feeder cell lines such as MS5 (see image)

	[Enlarge Image] Derivation of midbrain DA neurons from human ES cells

We have developed protocols for the efficient generation of neural progeny from various human ES cell lines. Neural induction can be achieved with several strategies, such as the formation of embryoid bodies followed by growth in serum-free medium; co-culture with stromal feeder cells; or via overgrowth and manual selection. Specific types of neurons can be induced by exposure to factors that control the development of specific brain regions of interest.

Other proteins (cytokines) can be used to bias differentiation into glial versus neuronal cell types. Genetic modification of human ES cells will allow introduction of foreign genes for cell labeling in transplantation studies or for the local production of therapeutic proteins.