Multipotency of purified, transplanted globose basal cells in olfactory epithelium

Abstract

By comparison with the rest of the nervous system, the olfactory epithelium has an unparalleled ability to renew and repair itself throughout life. However, the identity and capacity of the various types of progenitor cells that underlie that ability are not well established. We used selective isolation, transplantation, and engraftment of various types of marker-labeled cells into the epithelium of methyl bromide-lesioned, unmarked host mice to dissect progenitor cell capacity. Globose basal cells were purified from other potential progenitors using the monoclonal antibody GBC-2 (GBC, globose basal cell) and fluorescence activated cell sorting. Transplanted globose basal cells engraft and, in aggregate, give rise to globose basal cells, neurons, sustentacular cells, and several other kinds of non-neuronal cells. Individual clones, derived from single engrafted globose basal cells, can consist of a mixture of neurons and non-neuronal cells, only neurons, or only non-neuronal cells. Neurons that arise after transplantation mature to the point of expressing odorant receptors and olfactory marker protein and of projecting axons to the olfactory bulb. In contrast, other kinds of epithelial cells are neither neurogenic nor multipotent. For example, sustentacular and duct cells give rise only to themselves after transplantation. Furthermore, horizontal basal cells do not engraft in mice, in which the endogenous population is spared after lesion. Thus, some subtype(s) of GBC is a multipotent progenitor cell, whose multipotency is activated after destruction of both neurons and non-neuronal cells. The results suggest that progenitor cell transplantation may prove useful as a therapeutic modality as well as an analytical tool.

Identification and molecular regulation of neural stem cells in the olfactory epithelium

“…1A and [7]), these findings also imply that this putative stem cell lies among the GBCs. This idea is supported by recent experiments in which purified GBCs, transplanted into the OE of methyl bromidelesioned host mice, appear to give rise to both ORNs and SUS cells [35].…”

Adult c‐Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons

“…As in other selfrenewing tissues, it is the presence of stem and progenitor cells that underlie the regenerative capacity. OE basal layers contain a heterogeneous progenitor population (Goldstein and Schwob, 1996;Goldstein et al, 1998;Chen et al, 2004;Leung et al, 2007;Fletcher et al, 2011), and the niche signals regulating renewal and differentiation remain incompletely understood.…”

Notch 2 and Notch 1/3 segregate to neuronal and glial lineages of the developing olfactory epithelium

“…Additional GBCs represent immediate neuronal precursors (INPs), which divide only once or twice to generate immature receptor neurons (iORNS), and express the proneurogenic factors Ngn1 and NeuroD. Sus cells can also be generated from GBCs following methylbromide-induced injury to the OE (Schwartz Levey et al, 1991;Guillemot et al, 1993;Cau et al, 1997;Huard et al, 1998;Suzuki et al, 2003;Chen et al, 2004). In the lamina propria, OECs, derived from CNS progenitors, are thought to be generated through a glia-restricted precursor (GRP) amplification step, but these cells have yet to be identified in the developing LP.…”