A New Role for Glia: Generation of Neurons!

Abstract

Perhaps the most important step forward is that, for the first time, it is possible to prospectively identify at least some multipotent neural stem cells. Previously, a brain cell could only be identified as a stem cell retrospectively, by showing that it could generate multiple cell types and self-renew. Now, by isolating ependymal cells or SVZ astrocytes, it may be possible to obtain enriched neural stem cells. An important caveat, however, is that so far only 6% of the ependymal cells and about 10% of the SVZ astrocytes behave like stem cells in an in vitro assay. The small percentages might mean that only a subset of these glial cell types are in fact stem cells or might just reflect nonoptimal culture conditions.A far higher degree of enrichment, however, has just been achieved for the stem cells that generate the peripheral nervous system (Morrison et al. 1999xMorrison, S., White, P., Zock, C., and Anderson, D. Cell. 1999; 96: 737–749Abstract | Full Text | Full Text PDF | PubMedSee all ReferencesMorrison et al. 1999). Using FACS sorting, Sean Morrison and David Anderson were able to prospectively identify and isolate neural crest stem cells to greater than 80% purity. They transplanted the purified stem cells in vivo, where they survived and generated both neurons and glia. Moreover, by in vivo BrdU labeling experiments, they showed that the majority of the identified cells self-renew in vivo as well as in vitro. These experiments come the farthest to date in establishing that a given prospectively identified cell is actually a neural stem cell. But to definitively establish that any given cell type is truly a neural stem cell, it needs to be established that the prospectively identified cells are capable of extensive, though not necessarily sustained, self-renewal in vivo after transplantation, a goal not yet attained for any prospectively identified neural cell. An important criterion for stem cell identification in the hemopoietic system is that the transplanted cells be capable of reconstituting the entire tissue. This is probably not a reasonable criterion in the CNS as it is far from clear that the brain arises from a single stem cell type.Nonetheless our newfound ability to begin to prospectively identify neural stem cells opens an exciting new era for future neural stem cell work, as was true when hemopoetic stem cells were first identified and purified. By analyzing purified populations of neural stem cells, we can at last characterize their molecular and developmental properties and can also investigate whether they give rise to glial tumors. If we can figure out how to identify and purify human neural stem cells, the potential for gene therapy and neural cell replacement will be enormous.