Adult neural stem cells from the mouse subventricular zone are limited in migratory ability compared to progenitor cells of similar origin.
The subventricular zone (SVZ) in the forebrain is the largest source of neural stem cells and progenitor cells in the adult CNS. To assess the ability of adult neural stem cells to survive, differentiate and migrate, we have compared the behavior of dissociated, neurosphere-derived stem cells with that of progenitor cells in transplantation experiments. This ability was first tested in vivo, offering the stem cells the possibility to migrate along the rostral migratory stream (RMS), their specific pathway. In addition, the differential behaviors of the two classes of cells were also compared in vitro by grafting them into organotypic slice cultures containing either tangential (embryonic cerebral cortex) or radial (early postnatal cerebellar cortex) migratory routes. Most of the grafted adult neurosphere-derived stem cells survived and integrated in vivo, and a proportion of them differentiate into neurons, oligodendrocytes or astrocytes. However, they were unable to migrate along the RMS and remained in the vicinity of the injection site. In contrast, SVZ progenitor cells were able to migrate toward the olfactory bulb and, once there, to acquire the phenotype of granule cells, as previously reported. In vitro, neural stem cells exhibited a better migratory ability, although they only migrated for short distances, particularly, in forebrain slices. Nevertheless, the average distance covered by progenitor cells was a two-fold longer than that covered by neural stem cells, corroborating that this class of more specified cells has higher migratory ability. These results suggest that the in vitro conditions of expanding SVZ-derived stem cells, required to maintain them in an immature stage might modify their intrinsic properties, preventing their differentiation into neuroblasts and their subsequent migration.
INSERM U-106, Laboratoire de Neuromorphologie, Développement et Evolution, Hôpital de la Salpétrière, 75013 Paris, France.
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D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development / Q000637:transplantation; D002552:Cerebral Ventricles / Q000166:cytology* / Q000254:growth & development; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013997:Time Factors; D019737:Transplants; D014404:Tubulin / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D018991:Myelin Proteolipid Protein; D014404:Tubulin; C462941:beta3 tubulin, mouse; D049452:Green Fluorescent Proteins; D010751:Phosphopyruvate Hydratase