Abstract: |
Embryonic stem (ES) cells serve as universal building blocks for the generation of all somatic cell types including cells of the CNS. However, in vitro analysis of ES cell progeny has been difficult due to our inability to effectively harness the enormous differentiation potential of the cells. Recently, we have reported the efficient generation of midbrain dopamine neurons from mouse ES cells. A five-step differentiation protocol converts ES cells into differentiated CNS progeny via the sequential generation of embryoid bodies, neural plate-like cells, neural progenitors and immature neurons and glial cells. An alternative technique is based on the use of stromal cell feeders that directly induces dopaminergic differentiation of mouse ES cells. Here, we demonstrate that stromal feeder-mediated ES cell differentiation is not limited to the generation of dopamine neurons but - similar to the sequential five-step technique - allows the generation of a wide range of specialized neuronal and glial cell types including dopamine, serotonin, GABA, glutamate and acetylcholine neurons. ES cell differentiation systems provide a powerful in vitro assay for elucidating the molecular determinants of cell fate and allow the generation of unlimited numbers of specialized cells for brain repair. |