Contribution of olfactory neural stem cells to tissue maintenance and regeneration.
The olfactory neuroepithelium undergoes continual neurogenesis and, after extensive lesions, fully regenerates to maintain sensory function. The stem cell population underlying this regenerative capacity remains elusive. Here we show that mouse horizontal basal cells (HBCs) function as adult olfactory neuroepithelium neural stem cells and examine their distinct dynamics in olfactory neuroepithelium maintenance and regeneration. Fate-mapping analysis after olfactory neuroepithelium lesioning shows that HBCs are competent to regenerate both neuronal and non-neuronal olfactory neuroepithelium lineages. HBCs serve as a reservoir of long-lived progenitors that remain largely quiescent during normal neuronal turnover or even after acute, selective loss of mature neurons. Under these conditions, previously identified progenitors are largely responsible for tissue maintenance. Yet after extensive injuries that deplete resident neuronal precursors, HBCs transiently proliferate and their progeny fully reconstitute the neuroepithelium. Our data support a new model of adult neurogenesis in which distinct cell populations mediate normal neuronal turnover and neuronal replacement upon traumatic injury.
Leung
Cheuk T
CT
Center for Sensory Biology and the Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, PCTB 801, Baltimore, Maryland 21205, USA.
Coulombe
Pierre A
PA
Reed
Randall R
RR
D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D046569:Neuroepithelial Cells / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology*; D051842:Olfactory Marker Protein / Q000378:metabolism; D009833:Olfactory Pathways / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000633:toxicity; D013997:Time Factors
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; D013629:Tamoxifen; C499317:Ascl1 protein, mouse; C030659:K antigens; C016601:afimoxifene; C486336:Neurog1 protein, mouse