Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain

The mammalian brain contains a population of neural stem cells (NSC) that can both self-renew and generate progeny along the three lineage pathways of the central nervous system (CNS), but the in vivo identification and localization of NSC in the postnatal CNS has proved elusive. Recently, separate studies have implicated ciliated ependymal (CE) cells, and special subependymal zone (SEZ) astrocytes as candidates for NSC in the adult brain. In the present study, we have examined the potential of these two NSC candidates to form multipotent spherical clones-neurospheres-in vitro. We conclude that CE cells are unipotent and give rise only to cells within the glia cell lineage, although they are capable of forming spherical clones when cultured in isolation. In contrast, astrocyte monolayers from the cerebral cortex, cerebellum, spinal cord, and SEZ can form neurospheres that give rise both to neurons and glia. However, the ability to form neurospheres is restricted to astrocyte monolayers derived during the first 2 postnatal wk, except for SEZ astrocytes, which retain this capacity in the mature forebrain. We conclude that environmental factors, simulated by certain in vitro conditions, transiently confer NSC-like attributes on astrocytes during a critical period in CNS development.