Temporal establishment of neural cell identity in vivo and in vitro.

Understanding cell fate specification is particularly useful because it enables biologists to generate specific neural cell types for treating currently untreatable neurological diseases. Traditionally, lineage-specific progenitors are generated in vitro from pluripotent cells, after which they may be channeled into more mature cell types in a stage-specific manner, which is similar to the way cells behave during development. However, the emergence of induced pluripotent stem cells means that specific cell types can be generated directly from fibroblasts or other somatic cell types, thus bypassing all of the necessary steps that happen in vivo. Based on this information, the present review first explores the regulatory circuitry that drives cell fate specification over time in vivo. In particular, it describes how the appearance of specific neuronal and glial cell types is governed by an intrinsic biological clock, followed by a discussion of how this can be achieved through the temporal expression of intracellular regulators in relation to cell-specific Dnase I hypersensitivity sites, promoters and enhancers. Cell fate acquisition in vitro was then examined in an attempt to evaluate whether the temporal regulation neural cell fate in vivo is still relevant to the generation of reprogrammed neural stem cells and neurons.