Unraveling the Role of Ensheathing Cells and Perineural Fibroblasts in Olfactory Neurogenesis.

Abstract

During development and following injury-induced neurogenesis, olfactory ensheathing cells (OECs) envelope the axon bundles of sensory neurons and support their growth to the glomerular destinations in the olfactory bulb. Transplantation of OECs to various neuronal injury locations showed a reparative impact; however, there was huge variability. By combining mRNA sequencing with bioinformatics analysis and immunohistochemistry, we characterized the cellular and molecular biological properties of OECs of the lamina propria and their response to neuronal injury. We found that OECs do not express NGFR (p75) under steady state conditions, questioning the common approach of isolating OECs with NGFR antibodies. While OECs express a peculiar combination of markers of different types of glial cells, they are strikingly similar to satellite glia cells of the dorsal root ganglion; for example, they showed marked upregulation of genes involved in lipid metabolism during neuronal regeneration. Similar to satellite glia cells and unlike Schwann cells, adult OECs did not proliferate in response to injury. Like endothelial cells at the blood-brain barrier and unlike other glia types, OECs showed extensive connections via the tight junction protein Claudin 5. Furthermore, OECs lack water channels, which probably explains why they sustain a stable environment after olfactory epithelium ablation. Regulation of the extracellular osmolarity seems to involve Aquaporin 1 in perineural fibroblasts together with high levels of KCNJ10, Na⁺K⁺ATPase, and gap junctions in OECs. Optimizing the clinical uses of these unique glia cells is probably made easier by this thorough characterization of marker gene expression in steady state and during neurogenesis.