Stem cell progenitors of the olfactory epithelium: role of horizontal basal cells in the maintenance of neurogenesis in vitro
Data
2025-02-27
Autores
Gameiro, Juliana Gutschow
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Resumo
Background: The sense of smell is essential for human survival and well-being, influencing both sensory perception and psychological health. The olfactory epithelium (OE), which detects odorants through olfactory sensory neurons (OSNs), is continuously exposed to the external environment, making it highly susceptible to damage. Despite this vulnerability, the OE exhibits lifelong neurogenesis, primarily driven by two stem cell populations: globose basal cells (GBCs) and horizontal basal cells (HBCs). Due to the OE’s deep anatomical location and individual variability, in vivo studies pose challenges, highlighting the need for in vitro models to advance olfactory regeneration research. However, a reliable in vitro system that accurately mimics the OE’s cellular organization and microenvironment remains lacking. Objectives: This study aimed to develop a novel organoid culture method for the OE and utilize it to investigate the role of the olfactory niche in neurogenesis. Additionally, a literature review was conducted to clarify misconceptions regarding olfactory stem cells. Methods & Results: Mouse OE tissue was harvested, dissociated, and cultured in a chemically defined medium that promoted organoid formation. Immunofluorescence staining and single-cell sequencing confirmed that the organoids recapitulated in vivo neurogenesis and contained HBCs, GBCs, and immature OSNs. Lineage tracing revealed that while HBCs were present in most organoids, they remained largely quiescent. Fluorescence-activated cell sorting (FACS) to obtain HBCs or GBCs for isolated or mixed cultures demonstrated that HBCs were essential for organoid formation. Further analysis revealed that this dependency was primarily mediated through direct cell contact, with a lesser contribution from soluble factors. The literature review provided a comprehensive distinction between olfactory stem cell types, addressing common misclassifications. Conclusion: This thesis work establishes a three-dimensional OE organoid model that closely replicates in vivo neurogenesis while preserving key stem cell populations. Findings emphasize the essential role of HBCs in maintaining the organoid niche and supporting neurogenesis despite their predominantly quiescent state. This model provides a valuable platform for future research on olfactory regeneration and stem cell dynamics
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Olfactory epithelium, Olfactory stem cells, Organoid, Horizontal basal cell, Niche, Neurogenesis, Olfactory organoids