The human airway epithelial basal cell transcriptome.

The human airway epithelial basal cell transcriptome.
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DOI:
10.1371/journal.pone.0018378
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发表时间:
2011-05-04
期刊:
影响因子:
3.7
通讯作者:
Crystal RG
Crystal RG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hackett NR;Shaykhiev R;Walters MS;Wang R;Zwick RK;Ferris B;Witover B;Salit J;Crystal RG

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人的呼吸道上皮由纤毛细胞、分泌细胞、柱状细胞和基底细胞4种主要细胞类型组成。在自然周转和对损伤的反应中,呼吸道基底细胞作为其他类型呼吸道细胞的干/祖细胞发挥作用。本研究的目的是通过定义人类呼吸道上皮细胞群体的基因表达特征来更好地了解人类呼吸道上皮细胞生物学。取健康非吸烟者的呼吸道上皮,采用支气管刷取法。用微阵列检测从呼吸道上皮中纯化的基底细胞的转录组,并与分化的呼吸道上皮的转录组进行比较。这项分析确定了“人类呼吸道基底细胞特征”为1,161个独特的基因,其在基底细胞中的表达水平是分化上皮细胞的5倍。在体外,当基底细胞分化为纤毛状的呼吸道上皮时,基底细胞的特征被抑制。基底细胞特征与来自其他人类组织的基底样细胞表达的基因以及与小鼠呼吸道基底细胞表达的基因重叠。与自我调节以及向其他类型的呼吸道细胞发出信号一致,人类呼吸道基本细胞的特征是编码细胞外基质成分、生长因子和生长因子受体的基因,包括与EGF和VEGF通路相关的基因。有趣的是,虽然基底细胞特征与其他器官的基底样细胞特征重叠,但人类呼吸道基础细胞特征具有以前与这种细胞类型不相关的特征,包括编码细胞外基质成分的独特基因模式、G蛋白偶联受体、神经活性配体和受体以及离子通道。本研究中确定的人类呼吸道上皮基本细胞特征为人类呼吸道上皮干/祖细胞的分子表型和生物学提供了新的见解。
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 human airway epithelial basal cell biology by defining the gene expression signature of this cell population. Bronchial 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. 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.
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