Human ESC-derived neural rosettes and neural stem cell progression

Neural stem cells (NSCs) are defined by their ability to self-renew while retaining differentiation potential toward the three main central nervous system (CNS) lineages: neurons, astrocytes, and oligodendrocytes. A less appreciated fact about isolated NSCs is their narrow repertoire for generating specific neuron types, which are generally limited to a few region-specific subtypes such as GABAergic and glutamatergic neurons. Recent studies in human embryonic stem cells have identified a novel neural stem cell stage at which cells exhibit plasticity toward generating a broad range of neuron types in response to appropriate developmental signals. Such rosette-stage NSCs (R-NSCs) are also distinct from other NSC populations by their specific cytoarchitecture, gene expression, and extrinsic growth requirements. Here, we discuss the properties of R-NSCs within the context of NSC biology and define some of the key questions for future investigation. R-NSCs may represent the first example of a NSC population capable of recreating the full cellular diversity of the developing CNS, with implications for both basic stem cell biology and translational applications in regenerative medicine and drug discovery.