Intrinsic differences distinguish transiently neurogenic progenitors from neural stem cells in the early postnatal brain

Recent reports of stem cell plasticity have led to the suggestion that there are few intrinsic differences between precursor cells, and that environment dictates fundamental cellular properties such as differentiation potential. This suggestion has been buoyed by other work suggesting that apparent in vivo differences between neural precursor cells are lost when placed in a culture environment. We sought to further test this hypothesis by comparing neural precursors present in various neural tissues during the early postnatal period. Precursors from three postnatal actively neurogenic regions and three postneurogenic regions (cerebral cortex, lateral striatum, and optic nerve) were assayed at postnatal day 1, day 10, and adulthood, and compared to well-characterized ventricular subependymal neural stem cells. In contrast to stem cells that remain multipotential throughout life, the progenitor cells become restricted in a time- and region-dependent manner to an exclusively glial-producing phenotype, a phenomenon that occurs both in vitro and in vivo. Transcription factors associated with neural precursor identity are expressed regardless of brain region of origin or time in vitro. Environmental coculture manipulations are only able to rescue neurogenesis in olfactory bulb precursors but not other restricted progenitors. Thus, in contrast to the views that the in vitro environment has a homogenizing effect on distinct neural precursors, our data suggest that robust intrinsic differences with respect to self-renewal and continued neuron production exist between neural precursors from different brain regions. These differences are evident in vitro and in vivo.