Neural crest-derived horizontal basal cells as tissue stem cells in the adult olfactory epithelium

Horizontal basal cells (HBCs) have garnered attention as tissue stem cells of the olfactory epithelium (OE); however, these cells' exact lineage and their contributions to OE regeneration remain unknown. Neural crest-derived cells (NCDCs) have been shown to possess stem cell properties and to participate in the normal development of the OE. However, the contributions of NCDCs to both normal and regenerating adult OE remain unclear. In this study, we investigated the contribution of NCDCs to the OE, focusing particularly on HBCs. Using immunohistochemistry, we observed the OE of P0-Cre/EGFP mice expressing EGFP-tagged NCDCs at several stages of normal development along with regenerated OE following methimazole treatment. We observed EGFP expression in the HBCs, sustentacular cells (SUSs), Bowman's glands, olfactory receptor neurons (ORNs), and olfactory ensheathing cells of 6-week-old mice. No ectopic Cre expression was identified. Although HBCs at late embryonic stages were placode-derived (i.e., EGFP-negative), we found that EGFP+ HBCs alternatively increased with the decrease of placode-derived HBCs during maturation. In regenerated OE, the percentages of neural crest-derived ORNs and SUSs significantly increased compared with normal OE. These results suggest that NCDCs contribute greatly to the adult HBC population and that they are important for the maintenance of the OE.