Abstract
BackgroundThe 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 human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Methodology/Principal FindingsBronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the 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 differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of 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, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.Conclusion/SignificanceThe human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.
Highlights
The airway epithelium, a continuous pseudostratified population of cells lining the dichotomously branching airways, provides the barrier function that defends against inhaled gases, particulates, pathogens and other xenobiotics [1,2,3]
Conclusion/Significance: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium
Cell counting confirmed that differentiated cells were undetectable in cytospins of basal cells stained with markers for various cell types including two markers for ciliated cells (b-tubulin IV, 0/500 positively stained cells; dynein intermediate chain 1, 0/500), secretory cell marker, mesenchymal cell marker (N-cadherin, 0/500) and two neuroendocrine cell markers [chromogranin A, 0/1000; calcitonin-related polypeptide alpha (CGRP), 0/1000]
Summary
The airway epithelium, a continuous pseudostratified population of cells lining the dichotomously branching airways, provides the barrier function that defends against inhaled gases, particulates, pathogens and other xenobiotics [1,2,3]. As part of normal epithelial turnover and repair, the basal cells differentiate into the ciliated cells that help cleanse the surface of the airways, and secretory cells that produce mucins and other products that contribute to the extracellular apical barrier [1,6,8]. This process can be recapitulated by culture on air-liquid interface (ALI), where undifferentiated basal cells differentiate into ciliated and secretory cells [9,10,11,12,13,14]. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population
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