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 - Archive ouverte HAL Access content directly
Journal Articles Molecular Biology Reports Year : 2021

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

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Pierre de La Grange
  • Function : Author
Ariane Jolly
  • Function : Author
Charlotte Courageux
  • Function : Author
Chamseddine Ben Brahim
  • Function : Author

Abstract

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 (EMT)-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. Methods and results: We reanalyzed a gene expression dataset that we generated from COPD and normal primary bronchial basal progenitor cells knocked down for Slug/Snail2 gene. Among the genes that we identified to be repressed downstream of Slug/Snail2 in COPD, we selected those responding to differentiation and TGF-β. The large majority of these genes are upregulated with differentiation but repressed by TGF-β. Pathway and ontology enrichment analysis revealed a set of genes coding for transcription factors involved in stem cell maintenance that are repressed downstream of Slug/Snail2 and by TGF-β in COPD but not normal basal progenitor cells. We also reveal a link between Slug/Snail2 expression and the repressive effect of TGF-β on these stem cell maintenance genes. Conclusion: Our work brings a new insight and molecular perspective to the exhaustion of basal stem/progenitor cells observed in the airway epithelium of COPD patients, revealing that stem cell maintenance genes are repressed in these cells, with TGF-β and Slug/Snail2 being involved in this deregulation.
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hal-03427249 , version 1 (13-11-2021)

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  • HAL Id : hal-03427249 , version 1

Cite

Pierre de La Grange, Ariane Jolly, Charlotte Courageux, Chamseddine Ben Brahim, Pascale Leroy. 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. Molecular Biology Reports, 2021. ⟨hal-03427249⟩

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