Neural stem and progenitor cells in cancer and development

Abstract

Stem cells are unique cells that possess the capacities to both self-renew and give rise to multiple differentiated progeny. There exist two major types of stem cells that help to create the nervous system: CNS stem cells which produce the neurons and glia of the central nervous system and neural crest cells which produce not only the neurons and glia of the peripheral nervous system, but also structures such as the craniofacial skeleton, cardiac outflow tracts, skin pigment cells, and sympathoadrenal cells. The mechanisms of self-renewal, migration, and differentiation of these two stem cell types have been studied in great detail. Yet despite such insight, much remains to be known about key aspects of neural stem cell development. First, it has long been thought that there might be a lineal relationship between CNS stem cells in human embryos or adults and primary brain tumors, particularly those malignancies occurring in children. To earn better insight into this possibility, I examined fresh pediatric brain tumors and found that they contained a subpopulation of cells with characteristics of neural stem cells that, at a clonal level, could recapitulate properties of the parental tumor. These tumor-derived progenitors shared genetic similarities with normal neural stem cells and could migrate and proliferate in vivo. Second, I have studied whether the late-migrating wave of neural crest cells and their derivatives originates from stem or progenitor cells resident in the embryonic spinal cord by culturing quail neural tube cells as neurospheres. I have found that these cells have the potential to generate melanocytes and possibly other neural crest derivatives both in vivo and in vitro after weeks in culture, suggesting that neural crest or melanocytic progenitor cells in the neural tubes of older embryos might contribute to the late-migrating neural crest populations. Taken together, my results in both model systems suggest that neural stem or progenitor cells that persist in the animal beyond early embryonic development play significant roles at later points in development and life, particularly in the continued development of the peripheral nervous system and the development of malignancies of the central nervous system.