Colony-forming progenitors from mouse olfactory epithelium: Evidence for feedback regulation of neuron production

The mammalian olfactory epithelium (OE) supports continual neurogenesis throughout life, suggesting that a neuronal stem cell exists in this system, In tissue culture, however, the capacity of the OE for neurogenesis ceases after a few days, In an attempt to identify conditions that support the survival of neuronal stem cells, a population of neuronal progenitors was isolated from embryonic mouse OE and cultured in defined serum-free medium, The vast majority of cells rapidly gave rise to neurons, which died shortly thereafter, However, when purified progenitors were co-cultured with cells derived from the stroma underlying the OE, a small subpopulation (0.07-0.1%) gave rise to proliferative colonies. A morphologically identifiable subset of these colonies generated new neurons as late as 7 days in vitro, Interestingly, development of these neuronal colonies was specifically inhibited when purified progenitors were plated onto stromal feeder cells in the presence of a large excess of differentiated OE neurons, These results indicate that a rare cell type, with the potential to undergo prolonged neurogenesis, can be isolated from mammalian OE and that stroma-derived factors are important in supporting neurogenesis by this cell, The data further suggest that differentiated neurons provide a signal that feeds back to inhibit production of new neurons by their own progenitors.