Today it would be difficult to consider adult neurogenesis without reference to endogenous NSCs and their niches. Although early researchers had determined that individual NVP-BGJ398 manufacturer transcription factors directed cell fate, as in MyoD for muscle, and had done pioneering experiments proving that oocyte proteins could dedifferentiate a somatic cell nucleus, they could not have imagined the explosion of reprogramming that now allows us to generate human

neural cells from induced stem cells and enables us to model nervous system diseases in entirely new ways. Progress at the basic research level has also been astonishing, and we are already witnessing the translation of NSC science, with several clinical trials ongoing and more in the planning stages. In the following Perspective, we will

review some of the milestones of the last 25 years in NSC research. Rather than providing a Linsitinib clinical trial comprehensive review of these advances, we intend to highlight the major events and discoveries that we feel have made the most important contributions to our field. In particular, we will focus on the shifts in the field around the concept of adult neurogenesis and stem cells in the adult brain, especially in the hippocampus. We will discuss the more recent development of methodologies for reprogramming and induced pluripotent stem cells (iPSCs) and outline our views on the promise of NSC-based approaches for the treatment of disease. Significant milestone advances and that have driven NSC research forward have been summarized in Table 1, and we have also provided a tools wish list that would enable researchers to address some key remaining questions concerning NSC biology (Table 2). The views here represent our personal perspectives on what has been particularly significant; we readily acknowledge that this only reflects a fraction of the interesting and important

work in the field, and we apologize to those whose work we have not had space to discuss and reference. As you read this Perspective, we hope to inspire you to imagine the conceptual advances and new applications of NSC research over the next 25 years. It is difficult to imagine how much in the dark we were about mammalian nervous system development back in the 1980s. One of the burning questions at that time was whether or not common progenitor cells for neurons and glia even existed. Stem cells were not generally considered a part of brain development but rather the building blocks of other, more plastic tissues. The tools available to us to address these fundamental questions were limited.