Abstract
Despite a remarkable regenerative capacity, recovery of the mammalian olfactory epithelium can fail in severely injured areas, which subsequently reconstitute as aneuronal respiratory epithelium (metaplasia). We contrasted the cellular response of areas of the rat epithelium that recover as olfactory after methyl bromide lesion with those undergoing respiratory metaplasia in order to identify stem cells that restore lesioned epithelium as olfactory. Ventral olfactory epithelium is at particular risk for metaplasia after lesion and patches of it are rendered acellular by methyl bromide exposure. In contrast, globose basal cells (GBCs, marked by staining with GBC-2) are preserved in surrounding ventral areas and uniformly throughout dorsal epithelium, which consistently and completely recovers as olfactory after lesion. Over the next few days, neurons reappear, but only in those areas in which GBCs are preserved and multiply. In contrast, parts of the epithelium in which GBCs are destroyed are repopulated in part by Bowman's gland cells, which pile up above the basal lamina. Electron microscopy confirms the reciprocity between gland cells and globose basal cells. By 14 days after lesion, the areas that are undergoing metaplasia are repopulated by typical respiratory epithelial cells. As horizontal basal cells are eliminated from all parts of the ventral epithelium, the data suggest that GBC-2(+) cells are ultimately responsible for regenerating olfactory neuroepithelium. In contrast, GLA-13(+) cells may give rise to respiratory metaplastic epithelium where GBCs are eliminated. Thus, we support the idea that a subpopulation of GBCs is the neural stem cell of the olfactory epithelium.