Summary: Researchers have developed a three-dimensional mouse organoid model to study how olfactory neurons regenerate. Their work reveals that a stem cell type previously thought to be largely inactive plays an important role in repairing smell-sensing tissue. The study shows that horizontal basal cells (HBCs), identified by KRT5 expression, actively support neuron formation in concert with globose basal cells (GBCs).
This accessible organoid model clarifies mechanisms that may underlie smell loss from aging, viral infections such as COVID-19, and other causes that impair stem cell function. Designed for labs with modest resources, it could be a stepping stone toward human olfactory organoids to screen treatments for anosmia and hyposmia.
Key Facts:
- Hidden Helpers: KRT5-positive HBCs, once considered dormant, are essential contributors to olfactory neuron regeneration.
- Aging Impact: Cells from older mice show reduced neuron production, likely linked to declines in the GBC population.
- Practical Tool: The protocol is low-cost and designed to be reproducible in many laboratories studying smell disorders.
Source: Tufts University
Researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences, together with collaborators, created a straightforward 3D mouse olfactory organoid to investigate how nerve tissue in the nose regenerates and why that capacity fails in disease and with age.
Unlike most neurons in the central nervous system, sensory neurons in the nasal cavity retain the ability to replenish themselves throughout life despite constant exposure to environmental insults. Viral infections such as COVID-19, chemical exposures, and the normal aging process can all reduce the function of these neurons or the ability of their progenitor cells to reproduce, producing partial or complete smell loss.
Published in Cell Reports Methods, the study uses the mouse organoid to map interactions between two stem cell types in the olfactory epithelium: horizontal basal cells (HBCs) and globose basal cells (GBCs). The authors report that these populations are not independent; instead, they interact in ways that promote the steady production of olfactory sensory neurons.
“Our data suggest HBCs and GBCs are interdependent,” says Brian Lin, senior author and research assistant professor in the Department of Developmental, Molecular and Chemical Biology. “HBCs, which we previously considered largely quiescent, appear to play a crucial supportive role in neuron production and tissue repair.”
Using cell markers, the team identified a subpopulation of HBCs defined by KRT5 expression that actively contributes to neurogenesis in the organoid. When the researchers selectively removed these KRT5-positive HBCs from cultures, the organoids’ ability to generate new neurons dropped markedly, indicating these cells are essential for the regenerative process.
The investigators also compared cells from mice of varying ages. “Cells from older mice produced fewer new neurons in our model,” Lin notes. The group hypothesizes that the decline reflects a shrinking GBC pool with age, and they plan follow-up studies to confirm this and to explore strategies to rejuvenate or bolster these progenitors.
An Easy-To-Use Model
Lead author Juliana Gutschow Gameiro, a former Ph.D. student visiting GSBS from the State University of Londrina in Brazil, prioritized developing a protocol that could be implemented in labs without specialized equipment. The result is a reproducible, low-cost organoid method that reduces barriers for researchers from diverse fields—especially those newly studying olfaction after the surge of interest following COVID-19-related smell loss.
“We designed the system so non-stem-cell specialists and labs with limited resources can study how olfactory neurons are formed and why that process breaks down,” Lin says. The approachable protocol should accelerate work into causes of smell disorders and potential interventions.
Next Step: A Human Organoid
A primary aim is to adapt findings from the mouse model into a human olfactory organoid suitable for drug screening and therapeutic development. Organoids can make preclinical research faster, cheaper, and potentially more predictive than whole-animal studies or standard cell cultures. While organoids exist for organs such as lungs and kidneys, a robust human olfactory organoid has not yet been established.
One challenge is obtaining pure human olfactory tissue. Clinical sampling requires anesthetizing volunteers and using a brush-like device inserted deep into the nasal cavity, which collects a mixture of respiratory and olfactory stem cells that can be difficult to separate. The team’s next goal is to develop a simple, cost-effective method to isolate human olfactory stem cells and support their growth in vitro.
Funding: This research was supported by the National Institutes of Health (awards R21 DC018681-01 and R01 DC017869-03), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil, the German Research Foundation (DFG) Walter Benjamin Program, and the Fritz Thyssen Foundation. Complete information on authors, methodology, and conflicts of interest is available in the published paper. The content reflects the authors’ views and not necessarily those of the funders.
About this olfaction and genetics research news
Author: Tara Pettinato
Source: Tufts University
Contact: Tara Pettinato – Tufts University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Quiescent horizontal basal stem cells act as a niche for olfactory neurogenesis in a mouse 3D organoid model” by Brian Lin et al., Cell Reports Methods.
Abstract
Quiescent horizontal basal stem cells act as a niche for olfactory neurogenesis in a mouse 3D organoid model
The olfactory epithelium is one of the few mammalian tissues that supports lifelong neuronal regeneration, yet it has been understudied. Our objectives were twofold: first, to provide a straightforward, reproducible methodology that avoids specialized animal models and fluorescence-activated cell sorting, lowering the barrier for other labs to adopt the model; and second, to advance practical in vitro screening approaches that could accelerate the development of treatments for olfactory dysfunction.