Regionally distinct neural stem cell populations in the mouse embryonic brain and spinal cord.

摘要

When I began this project I was interested in determining whether transplantation of spinal cord derived neural stem cells (NSCs) was better than cortical derived NSCs for treatment of chronic spinal cord injury, specifically a cauda equina injury. However, as I started these studies, I began to question the underlying assumption that there was a difference between cortical and spinal cord NSCs. Thus, the experiments presented here focus on determining whether cortical and spinal cord NSCs are different and elucidating what those differences are. There is a wide body of literature that has examined brain derived NSCs, however it is not clear whether the findings extend to NSCs from the spinal cord. In this dissertation, I have examined the mitogen responsiveness of spinal cord derived NSCs and found that spinal cord derived NSCs are responsive to bFGF throughout embryonic development but are not responsive to EGF until after embryonic day 11. Proliferation rates and mitogen responsiveness are similar between cortical and spinal cord derived NSCs throughout embryonic development. Although, these properties are similar between cortical and spinal cord derived NSCs, there are significant differences in gene expression patterns indicating that NSCs from the embryonic mouse are regionally specified.; Lewis X (LeX) expression has been used to enrich for NSCs from the brain, however it is not clear whether spinal cord NSCs can also be enriched based on LeX expression. I found that there is a population of cells in the embryonic spinal cord that does not express LeX but displays all of the characteristics of NSCs. The expression of cell cycle genes correlates with neurosphere forming ability, while genes associated with stem cell behaviors are expressed by LeX+ and LeX- cells from both cortical and spinal cord derived neurospheres.; These data indicate that there are regionally distinct NSC populations within the central nervous system (CNS) as well multiple populations within the spinal cord itself. Future studies should focus on understanding the mechanisms behind these differences in addition to ways to exploit them in order to stimulate endogenous NSCs following injury and make optimal candidate cells for transplantation following injury.