Key Points

Unlike cells in the central nervous system, sensory neurons in the nasal cavity have a remarkable ability to regenerate throughout life despite near-constant exposure to the outside environment.

Viral infections such as COVID-19, exposure to toxins, or even aging itself can diminish their function or the ability of these cells to replicate, which can lead to a partial or complete loss of smell.

The team of researchers devised a new, easy-to-create, three-dimensional olfactory tissue mouse model or organoid to help scientists better study how neurons are continually formed in the nose and why this process might decline in disease and aging.

Their research, published recently in Cell Reports Methods, uses this mouse model to show how two types of stem cells in the nose, called horizontal basal cells (HBCs) and globose basal cells (GBCs), communicate and support each other to develop new smell-sensing nerve tissue.

"Our research suggests that these two stem cells may be interdependent," says Brian Lin, senior author on the study and a research assistant professor in the Department of Developmental, Molecular and Chemical Biology.

"One type that we thought was largely dormant -- HBCs -- may actually play a crucial role in supporting the production of new neurons and the repair of damaged tissue," added Lin.

Using this model, the team identified a specific subpopulation of HBCs, marked by their production of the protein KRT5, that actively support the generation of new olfactory neurons.

The researchers observed that these particular HBCs play a key role in the formation of the organoids, and they found that when these cells were selectively depleted from the organoid cultures, the generation of new neurons was significantly impaired.

These results suggest that these stem cells, once thought to be dormant, are essential players in the regenerative process.

"We also looked at cells from mice of different ages and grew them in the model. We found a decline in the ability of the older mice cells to generate new neurons. We think this is due to a decrease in the GBC population as we age, but we need to do more work to test this hypothesis and if so, develop ways to rejuvenate them," said Lin.

Lin says she was dedicated to developing a model that was easy to create in labs with limited funds and equipment.

The ultimate goal is to use this mouse-tissue model of olfactory sensory neurons as a pathway to developing a human organoid that can be used to screen drugs to treat people whose sense of smell is significantly diminished or gone.

- ANI