Neurobiology Select

Neural stem cells are widely studied for their therapeutic potential and for the insight they reveal into the mechanisms of brain development. The latest advances in neural stem cell research are the topic of this issue's Neurobiology Select. These findings include a simple protocol for reprogramming human neural stem cells to pluripotency and a report demonstrating that transplanted neural stem cells can have a therapeutic benefit by promoting the survival of endogenous neurons. Other work explores the mechanisms regulating neurogenesis in vivo, including the impact of transcriptional regulation, cell-cycle duration, and chromatin remodeling. Making human induced pluripotent stem (iPS) cells just got substantially easier. Kim et al. (2009) now show that human neural stem cells (NSCs) can be coaxed into pluripotency following the introduction of a single factor, the transcription factor OCT4. In prior work these authors demonstrated that mouse adult neural stem cells could be reprogrammed to pluripotency by the introduction of murine Oct4 alone. Their latest efforts bridge the species gap, providing a simpler means with which to create lines of human iPS cells for possible therapeutic uses. They show that the ingredients of the now famous four factor cocktail (OCT4, SOX2, c-Myc, and KLF4) are well-represented in neural stem cells, with all but OCT4 being expressed endogenously. Adding OCT4 to this pre-made mix completes the potent brew. This technical achievement should further intensify the search for compounds that imitate the effects of pluripotency factors, most notably OCT4. In addition, these finding add to a growing body of evidence that endogenously expressed pluripotency factors have the capacity to contribute to the generation of iPS cells. A potential corollary is that expression profiling should offer guidance as to which pluripotency factors might be needed to transform other tissue-specific stem cells into iPS cells. To have a therapeutic benefit, transplanted neural stem cells may not need to replace lost or damaged neurons. According to surprising new work by Tamaki et al. (2009), transplanted neural stem cells could instead foster an environment that is more supportive to the survival of endogenous neurons teetering on the brink of death. The authors report that human neural stem cells (grown as neurospheres) are neuroprotective when transplanted into the brains of embryonic mice lacking the enzyme palmitoyl protein thoiesterase-1(Ppt1). In humans the loss of PPT1 leads to the fatal neurodegenerative disease infantile neuronal ceroid lipofuscinosis (INCL), and Ppt knockout mice recapitulate many features of the …