The Human Airway Epithelial Basal Cell Transcriptome

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.

**背景** 人类气道上皮包含四种主要细胞类型：纤毛细胞、分泌细胞、柱状细胞及基底细胞（basal cells）。在自然更新及损伤应答过程中，气道基底细胞作为其他气道细胞类型的干/祖细胞发挥功能。本研究旨在通过明确该细胞群体的基因表达特征，深入解析人类气道上皮基底细胞的生物学特性。

**方法与主要结果** 研究通过支气管刷检术从健康非吸烟者体内获取气道上皮组织。利用基因芯片（microarrays）分别检测纯化得到的气道上皮基底细胞与分化成熟气道上皮的转录组，并进行对比分析。本分析明确了“人类气道基底细胞特征基因集”：即在基底细胞中表达量较分化上皮高5倍以上的1161个独特基因。当基底细胞在体外分化为纤毛气道上皮时，该特征基因集的表达受到抑制。该特征基因集与其他人体组织中类基底细胞的表达基因，以及小鼠气道基底细胞的表达基因均存在重叠。与基底细胞的自我调控及对其他气道细胞类型的信号调控功能相符，人类气道基底细胞特征基因集以编码细胞外基质成分、生长因子及生长因子受体的基因为核心特征，其中包含与表皮生长因子（EGF）及血管内皮生长因子（VEGF）通路相关的基因。值得注意的是，尽管该特征基因集与其他器官的类基底细胞特征基因存在重叠，但人类气道基底细胞特征基因集还具备此前未在该类细胞中发现的独特特征，包括编码细胞外基质成分、G蛋白偶联受体、神经活性配体及受体以及离子通道的独特基因模式。

**结论与意义** 本研究鉴定得到的人类气道上皮基底细胞特征基因集，为解析人类气道上皮干/祖细胞的分子表型及生物学特性提供了全新的研究视角。