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Plasticity of airway epithelial cell transcriptome in response to flagellin.

ABSTRACT: Airway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using whole-genome microarrays and RNA sequencing. We exposed monolayer and ALI AEC cultures to flagellin in vitro and analyzed the transcriptional response by microarray and RNA-sequencing. ELISA and RT-PCR were used to validate changes in select candidates. We found that AECs cultured in monolayer and ALI have strikingly different transcriptional states at baseline. When challenged with flagellin, monolayer AEC cultures greatly increased transcription of numerous genes mapping to wounding response, immunity and inflammatory response. In contrast, AECs in ALI culture had an unexpectedly muted response to flagellin, both in number of genes expressed and relative enrichment of inflammatory and immune pathways. We conclude that in vitro culturing methods have a dramatic effect on the transcriptional profile of AECs at baseline and after stimulation with flagellin. These differences suggest that epithelial responses to pathogen challenges are distinctly different in culture models of intact and injured epithelium.

SUBMITTER: Clark JG

PROVIDER: S-EPMC4323341 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Plasticity of airway epithelial cell transcriptome in response to flagellin.

Clark Joan G JG Kim Kyoung-Hee KH Basom Ryan S RS Gharib Sina A SA

PloS one 20150210 2

Airway epithelial cells (AEC) are critical components of the inflammatory and immune response during exposure to pathogens. AECs in monolayer culture and differentiated epithelial cells in air-liquid interface (ALI) represent two distinct and commonly used in vitro models, yet differences in their response to pathogens have not been investigated. In this study, we compared the transcriptional effects of flagellin on AECs in monolayer culture versus ALI culture using whole-genome microarrays and ...[more]

PMID: 25668187

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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.

Dataset Information

Plasticity of airway epithelial cell transcriptome in response to flagellin.

Publications

Plasticity of airway epithelial cell transcriptome in response to flagellin.

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