Science and Research

Airway derived emphysema-specific alveolar type II cells exhibit impaired regenerative potential in COPD

Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of chronic obstructive pulmonary disease (COPD) that is presently incurable. This therapeutic gap is largely due to a poor understanding of potential drivers of impaired tissue regeneration, such as abnormal lung epithelial progenitor cells, including alveolar type II (ATII) and airway club cells. We discovered an emphysema-specific sub-population of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single cell RNA-seq and in situ localisation revealed that asATII cells co-express the alveolar marker surfactant protein C (SPC) and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII sub-population derived from club cells was also identified in mouse COPD models using lineage labeling. Human and mouse ATII sub-populations formed 80-90% fewer alveolar organoids than healthy controls, indicating reduced progenitor function. Targeting asATII cells or their progenitor club cells could reveal novel COPD treatment strategies.

  • Hu, Y.
  • Hu, Q.
  • Ansari, M.
  • Riemondy, K.
  • Pineda, R.
  • Sembrat, J.
  • Leme, A. S.
  • Ngo, K.
  • Morgenthaler, O.
  • Ha, K.
  • Gao, B.
  • Janssen, W. J.
  • Basil, M. C.
  • Kliment, C. R.
  • Morrisey, E.
  • Lehmann, M.
  • Evans, C. M.
  • Schiller, H. B.
  • Königshoff, M.
Publication details
DOI: 10.1183/13993003.02071-2023
Journal: Eur Respir J
Work Type: Original
Location: CPC-M, UGMLC
Disease Area: COPD
Partner / Member: HMGU, UMR
Access-Number: 39147413

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