Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells

Abstract

We have infused replication-incompetent retroviral vectors into the nasal cavity of adult rats 1 day after exposure to the olfactotoxic gas methyl bromide (MeBr) to assess the lineage relationships of cells in the regenerating olfactory epithelium. The vast majority of the retrovirus-labeled clones fall into three broad categories: clones that invariably contain globose basal cells (GBCs) and/or neurons, clones that always include cells in the ducts of Bowman's glands, and clones that are composed of sustentacular cells only. Many of the GBC-related clones contain sustentacular cells and horizontal basal cells as well. Most of the duct-related clones contain gland cells, and some also include sustentacular cells. Thus, the destruction of both neurons and non-neuronal cells that is caused by MeBr activates two distinct types of multipotent cells. The multipotent progenitor that gives rise to neurons and non-neuronal cells is a basal cell, whereas the progenitor that gives rise to duct, gland, and sustentacular cells resides within the ducts, based on the pattern of sparing after lesion and the analysis of early regeneration by using cell type-specific markers. We conclude that the balance between multipotency and selective neuropotency, which is characteristic of globose basal cells in the normal olfactory epithelium, is determined by which cell types have been depleted and need to be replenished rapidly.

Distribution and severity of spontaneous lesions in the neuroepithelium and Bowman’s glands in mouse olfactory mucosa: age-related progression

“…If this is correct, the degeneration of the supporting cells, which is also frequently co-localized with the loss of ORNs (Figs. 4, 6), may also be involved in the process (Grubb et al 2007), since the supporting cells share a common developmental lineage (Huard et al 1998) and common functional roles (Krishna et al 1994;Yu et al 2005) with the acinar cells in Bowman's glands. We cannot, however, exclude the possibility that colocalization is merely coincidental, with accumulated environmental effects insulting both the neuroepithelium and Bowman's glands simultaneously.…”

Olfactory receptors

“…Such properties are possible due to the presence of multipotent neuronal precursors or globose basal cells in the olfactory epithelium [21 -24], and a particular cell type of the olfactory bulb that forms the OSN sheath, the olfactory ensheathing glial cells [25]. These multipotent progenitors are capable of producing nonneuronal cells as well as neurons [22]. Sustentacular cells, which originate from a different type of progenitor [22], are nonneuronal support cells that resemble glia.…”

“…These multipotent progenitors are capable of producing nonneuronal cells as well as neurons [22]. Sustentacular cells, which originate from a different type of progenitor [22], are nonneuronal support cells that resemble glia. These cells secrete detoxifying enzymes into mucus and isolate OSNs electrically.…”

Differential effects of olfactory toxicants on olfactory regeneration

“…The globose basal cells (GBCs) are the predominant proliferating population of cells, whereas the horizontal basal cells (HBCs) have a low mitotic index (Huard and Schwob 1995). GBCs are a heterogeneous population of cells that are generally believed to contain the immediate precursors of the olfactory neurons (Calof et al 1998;Huard et al 1998). The HBCs form envelopes around the bundles of olfactory axons before these leave the epithelium (Holbrook et al 1995).…”