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Highly regional generation and heterogenous differentiation of basal cells in mouse trachea

ABSTRACT: The airway epithelium comprises three major cell types: basal cells, secretory cells, and ciliated cells. Among these, basal cells serve as stem cells to generate other cell types. Airway basal cells have been recognized as functionally heterogeneous, with numerous studies with specific cell markers. The regional heterogeneity of basal cells has yet to be fully addressed, despite there being some in vitro evidence. In this study, we utilized a proliferation tracing system to demonstrate regional heterogeneity in the proliferative capacity and differentiation of airway basal cells. We found that dorsal basal cells possess a significantly higher proliferative capacity compared to their ventral counterparts. Further analysis revealed that the proliferating basal cells primarily constitute a subset previously identified as multipotent basal stem cells, which undergo symmetric division to expand the stem cell pool. Furthermore, we identified that the canonical Wnt signaling pathway plays a crucial role in maintaining the proliferation of these multipotent basal cells. These findings may have important implications for understanding airway repair mechanisms in disease and injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE318853 | GEO | 2026/04/28

REPOSITORIES: GEO

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Project description:Background. The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem / progenitor cells for the other airway cell types. The objective of this study is to better understand basal cell biology by defining the subset of expressed genes that characterize the signature of human airway epithelial basal cells. Methodology / Principal Findings. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium of healthy nonsmokers obtained by bronchial brushings in comparison to the transcriptome of the complete differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to the differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The human airway basal cell signature displayed extensive overlap with genes expressed in basal cells from other human tissues and murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the airway basal cell signature was characterized by genes encoding extracellular matrix components, and growth factors and growth factor receptors, including genes related to EGFR and VEGFR signaling. However, while human airway basal cells share similarity with basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, integrins, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion / Significance. The human airway epithelial basal cells signature identified in the present study provides novel insights into the ontogeny, molecular phenotype and biology of the stem / progenitor cells of the human airway epithelium. This study was designed to distinguish the transcriptome of the airway epithelium basal cell from that of differentiated airway epithelium. A basal cell signature was derived and analyzed for functional significance. The signature was also evaluated as basal cells differentiated into ciliated epithelium in vitro.

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Highly regional generation and heterogenous differentiation of basal cells in mouse trachea

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