Genes coding for transcription factors involved in stem cell maintenance are repressed by TGF-β and downstream of Slug/Snail2 in COPD bronchial epithelial progenitors.

Background: Basal stem/progenitor cells of airway epithelium from chronic obstructive pulmonary disease (COPD) patients have a decrease in differentiation and self-renewal potential. Our study aimed at identifying deregulations in the genetic program of these cells that could account for their exhaustion, focusing on genes downstream of the epithelial-mesenchymal transition-inducing transcription factor Slug/Snail2 and responding to transforming growth factor (TGF)-β. TGF-β is at higher levels in COPD patient lungs, plays a role in stem/progenitor cell fate and regulates the expression of Slug/Snail2 that is highly expressed in airway basal stem/progenitors.

Proliferation Genes Repressed by TGF-β Are Downstream of Slug/Snail2 in Normal Bronchial Epithelial Progenitors and Are Deregulated in COPD.

Slug/Snail2 belongs to the Epithelial-Mesenchymal Transition (EMT)-inducing transcription factors involved in development and diseases. Slug is expressed in adult stem/progenitor cells of several epithelia, making it unique among these transcription factors. To investigate Slug role in human bronchial epithelium progenitors, we studied primary bronchial basal/progenitor cells in an air-liquid interface culture system that allows regenerating a bronchial epithelium.