Quiescent horizontal basal stem cells act as a niche for olfactory neurogenesis in a mouse 3D organoid model.

Abstract

The olfactory epithelium contains two basal stem cell populations that facilitate the usually life-long ability for neuronal regeneration that is required for maintaining our sense of smell. Horizontal basal cells (HBCs) are generally quiescent and only become active after direct injury to the epithelium that eliminates more than just the olfactory sensory neurons (OSNs). Globose basal cells (GBCs) lie apical to HBCs and are solely responsible for the generation of olfactory neurons in the undamaged epithelium. Understanding how these two neurogenic stem cell populations are regulated as OSNs are replenished is hampered by a lack of robust culture models. Here, we report the development of a 3D mouse organoid model that recapitulates the neurogenic cascade, forming immature OSNs while maintaining both HBCs and GBCs in culture. We use this model to demonstrate that, despite their relative quiescence, HBCs form a critical niche for the emergence and composition of the organoid.