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Positional Identity of Branching-associated HOXB2 and B3 Gene Expression is Maintained by Adult Human Airway Epithelial Progenitor Cells

ABSTRACT: In the context that HOX mutant mice have profound deficits in airway branching morphogenesis, we asked whether the positional identity of HOX genes is maintained in the epithelium of the adult human tracheobronchial tree and if so, whether these positional differences are embedded in the stem/progenitor population derived from nonbranching vs branching airways. We found that 10 of 39 HOX genes are expressed in varying degrees in the nonbranching (trachea) or branching (large and small airways) human airway epithelium. Strikingly, HOXB2 and B3 were highly expressed in the trachea epithelium, but barely detectable in the branching airway epithelium. This difference in HOXB2 and B3 gene expression was embedded in the airway basal cell stem/progenitor population isolated from the trachea vs branching airways, and maintained during differentiation in vitro. Finally, HOXB2 and B3 expressions in the trachea vs branching airways correlated with the expression of a variety of other transcription and growth factors related to branching morphogenesis. The finding that the adult human airway epithelium expresses some HOX genes in a positional manner, with differences embedded in the transcriptomes of airway epithelial stem/progenitor cells, has implications for the use of stem/progenitor cells for applications relevant to lung regeneration.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31449 | GEO | 2024/06/05

REPOSITORIES: GEO

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Project description:Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84; and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction. The data provided here represents mRNA expression data from dissected whole trachea (distal and proximal ends were cut 3-4 cartilage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6N Tac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. Histologically, PND 0 trachea are normal, a tracheal mucus plug/obstruction develops around PND 3 and typically recedes to the intrapulmonary airways after PND 10, and the trachea is again histologically normal by PND 42. The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to airway mucus obstruction to be queried. The data presented for the trachea is part of a larger body of work evaluating gene expression in whole lung, trachea, and purified macrophages. 24 Total tracheal samples were analyzed; three from each timepoint. In our manuscript, we were most interested in changes between WT and Scnn1b-Tg mice, however, the data can also be used to evaluate changes in gene expression across time (PND 0, 3, 10, and 42). It should be noted that a significant difference in RNA expression quality parameters was noted for the 10 day trachea data.

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Positional Identity of Branching-associated HOXB2 and B3 Gene Expression is Maintained by Adult Human Airway Epithelial Progenitor Cells

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