Identification of a Repair-Supportive Mesenchymal Cell Population during Airway Epithelial Regeneration

Alena Moiseenko, Ana Ivonne Vazquez-Armendariz, Vahid Kheirollahi, Xuran Chu, Aleksandra Tata, Stefano Rivetti, Stefan Günther, Kevin Lebrigand, Susanne Herold, Thomas Braun, Bernard Mari, Stijn De Langhe, Grazyna Kwapiszewska, Andreas Günther, Chengshui Chen, Werner Seeger, Purushothama Rao Tata, Jin San Zhang, Saverio Bellusci, Elie El Agha

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue regeneration requires coordinated and dynamic remodeling of stem and progenitor cells and the surrounding niche. Although the plasticity of epithelial cells has been well explored in many tissues, the dynamic changes occurring in niche cells remain elusive. Here, we show that, during lung repair after naphthalene injury, a population of PDGFRα+ cells emerges in the non-cartilaginous conducting airway niche, which is normally populated by airway smooth muscle cells (ASMCs). This cell population, which we term “repair-supportive mesenchymal cells” (RSMCs), is distinct from conventional ASMCs, which have previously been shown to contribute to epithelial repair. Gene expression analysis on sorted lineage-labeled cells shows that RSMCs express low levels of ASMC markers, but high levels of the pro-regenerative marker Fgf10. Organoid co-cultures demonstrate an enhanced ability for RSMCs in supporting club-cell growth. Our study highlights the dynamics of mesenchymal cells in the airway niche and has implications for chronic airway-injury-associated diseases.

Original languageEnglish (US)
Article number108549
JournalCell reports
Volume33
Issue number12
DOIs
StatePublished - Dec 22 2020

Keywords

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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