The Human Airway Epithelial Basal Cell Transcriptome

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.

Protein Kinase D Promotes Airway Epithelial Barrier Dysfunction and Permeability through Down-regulation of Claudin-1

“…The airway epithelium is the first line of defense against inhaled gases, particulates, pathogens, and other potentially hazardous environmental stimuli (1)(2)(3). A growing body of evidence indicates that dysfunction of airway epithelial barrier is involved in the development and progression of various airway and lung diseases, such as asthma, lung injury and fibrosis, and chronic obstructive pulmonary disease (4 -10).…”

“…The airway epithelium is the first line of defense against inhaled gases, particulates, pathogens, and other potentially hazardous environmental stimuli (1)(2)(3). It has at least two major functions; (i) the epithelial cells form a tight barrier that physically isolates pathogens and particulates and selectively control the passage of ions, water, and other solutes (2); (ii) the epithelial cells produce chemokines and cytokines to recruit immune cells for dealing with immune responses or to limit foreign antigen invasion (2,3).…”

Lung organoids: current uses and future promise

“…The luminal cells are connected apically by junctional complexes and play a crucial role in forming a selectively permeable barrier between the external and internal environments of the lung. Genes characteristically expressed by basal cells include those encoding the transcription factor Trp63, the cytokeratin Krt5, integrin alpha 6 (Itga6), podoplanin (Pdpn; also known as T1alpha) and the transmembrane nerve growth factor receptor (Ngfr; also known as p75) (Hackett et al, 2011;Rock et al, 2009;Watson et al, 2015).…”

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

“…The cells are generally grown in monolayer culture on collagen I coated dishes using defined growth medium (e.g., BEGM from Clonetics) and can be expanded by 2-3 passages; early passage cells (P0) can be reliably cryopreserved without loss of viability for subsequent use. These cells express basal cell markers including cytokeratin 5 and the transcription factor p63 (Hackett et al, 2011a) and have been used as models of basal cells. al., 2010), mucociliary transport (Seagrave et al, 2012), airway toxicology (Mathis et al, 2013;Watson et al, 2010), electrophysiology (Hirsh et al, 2008), and bacterial and viral infection studies (Deng et al, 2014;Mitchell et al, 2011;Palmer et al, 2012;Ren and Daines, 2011;Ren et al, 2012).…”