Olfactory Horizontal Basal Cells Demonstrate a Conserved Multipotent Progenitor Phenotype

Abstract

Stem cells of adult regenerative organs share a common goal but few established conserved mechanisms. Within the neural stem cell niche of the mouse olfactory epithelium, we identified a combination of extracellular matrix (ECM) receptors that regulate adhesion and mitosis in non-neural stem cells [intercellular adhesion molecule-1 (ICAM-1), β₁, β₄, and α-1, -3, and -6 integrins] and on horizontal basal cells (HBCs), candidate olfactory neuro-epithelial progenitors. Using ECM receptors as our guide, we recreated a defined microenvironmentin vitrothat mimics olfactory basal lamina and, when supplemented with epidermal growth factor, transforming growth factor α, and leukemia inhibitory factor, allows us to preferentially expand multiple clonal adherent colony phenotypes from individual ICAM-1+ and ICAM-1+/β₁integrin+-selected HBCs. The most highly mitotic colony-forming HBCs demonstrate multipotency, spontaneously generating more ICAM-positive presumptive HBCs, a combination of olfactory neuroglial progenitors, and neurons of olfactory and potentially nonolfactory phenotypes. HBCs thus possess a conserved adhesion receptor expression profile similar to non-neural stem cells, preferential self-replication in anin vitroenvironment mimicking theirin vivoniche, and contain subpopulations of cells that can produce multiple differentiated neuronal and glial progeny from within and beyond the olfactory systemin vitro.