Stem Cells in the Developing and Adult Nervous System
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The fertilized egg is a totipotent stem cell that can produce all cell types of the organism, including the embryonic and the extraembryonic tissues. As development proceeds, cells lose their capacity to proliferate and differentiate into different cell types, and gain specialization. However, advances in stem cell biology have provided new insights into development and regenerative medicine. For example, neural stem/progenitor cells have been found to exist not only during embryonic development, but also in the adult nervous system of mammals. Moreover, although development of an organism proceeds irreversibly from embryo to adult with cells differentiating progressively toward specialized cell types, somatic cells can be artificially reprogrammed to adopt a different cell fate, as exemplified by induced pluripotent stem cells (iPS cells) and induced neuronal cells (iN cells). Complex 3D tissue including the retina, cortex and adenohypophysis can be generated from pluripotent stem cells in vitro. Notably, autologous transplantation of an iPS cell-derived retinal pigment epithelium sheet was carried out for patients with aged macular degeneration in Japan in 2014. iPS cell technology is opening a new era in regenerative medicine and drug discovery. Here, we summarize the current views of stem cell biology during embryogenesis and adult neurogenesis, and then discuss therapeutic potential of stem cells, focusing on retinal development and regeneration.
KeywordsNervous system Neuron Retina Embryonic stem cells Neural tube Induced pluripotent stem cells Induced neuronal cells Regeneration
We thank Yoshiki Sasai (RIKEN), Akinori Akaike (Kyoto University), Edward M. Callaway (The Salk Institute for Biological Studies), and E. J. Chichilnisky (The Salk Institute for Biological Studies) for their continued support and challenging discussions, and members of the Takahashi laboratory, the Sasai laboratory, the Akaike laboratory, the Callaway laboratory, and the Chichilnisky laboratory for stimulating discussions. We are grateful for support from the Leading Project for Realization of Regenerative Medicine (M.T.), Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (F.O.), the Japan Science and Technology Agency (F.O.), the Kanae Foundation for the Promotion of Medical Science (F.O.), the Naito Foundation (F.O.), the Hokuto Foundation for Bioscience (F.O.), Takeda Science Foundation (F.O.), the Astellas Foundation for Research on Metabolic Disorders (F.O.), the Brain Science Program of National Institutes of Natural Sciences (F.O.), and the Pioneer Fund (F.O.). We apologize to those authors whose articles, although relevant to this subject, have not been cited in this review due to space limitations.
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