In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus

To characterize the properties of adult neural stem cells (NSCs), we generated and analyzed Sox2-GFP transgenic mice. Sox2-GFP cells in the subgranular zone (SGZ) express markers specific for progenitors, but they represent two morphologically distinct populations that differ in proliferation levels. Lentivirus- and retrovirus-mediated fate-tracing studies showed that Sox2(+) cells in the SGZ have potential to give rise to neurons and astrocytes, revealing their multipotency at the population as well as at a single-cell level. A subpopulation of Sox2(+) cells gives rise to cells that retain Sox2, highlighting Sox2(+) cells as a primary source for adult NSCs. In response to mitotic signals, increased proliferation of Sox2 cells is coupled with the generation of Sox2(+) NSCs as well as neuronal precursors. An asymmetric contribution of Sox2(+) NSCs may play an important role in maintaining the constant size of the NSC pool and producing newly born neurons during adult neurogenesis.