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.
Mumm
J S
JS
Department of Anatomy, University of California, Irvine, College of Medicine 92697-1275, USA.
Shou
J
J
Calof
A L
AL
D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D002469:Cell Separation; D002478:Cells, Cultured; D051379:Mice; D009831:Olfactory Mucosa / Q000166:cytology*; D018034:Olfactory Receptor Neurons / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology