Molecular mapping of interstitial lung disease reveals a phenotypically distinct senescent basal epithelial cell population

• DOI: 10.1172/jci.insight.143626
• Publication Date: 2021-03-11T17:01:11Z
• Authors: Daryle J. DePianto; Jason A. Vander H...; Katrina B. Morshead; Kai-Hui Sun; Zora Modrusan; Grace Teng; Paul J. Wolters; Joseph R. Arron
• Keywords: Basal (medicine); Keratin 5

Compromised regenerative capacity of lung epithelial cells can lead to cellular senescence, which may precipitate fibrosis. While increased markers senescence have been reported in idiopathic pulmonary fibrosis (IPF), the origin and identity these senescent remain unclear, tools characterize context-specific human are lacking. We observed that marker p16 is predominantly localized bronchiolized structures scarred regions IPF systemic sclerosis-associated interstitial disease (SSc-ILD) tissue, overlapping with basal Keratin 5 17. Using vitro models, we derived transcriptional signatures programming specific different types interrogated a single-cell RNA-Seq data set from control, IPF, SSc-ILD tissue. identified population defined by, enriched for, candidate ILD enable future functional studies. Notably, gene expression significantly overlaps terminally differentiating stratified epithelia, where it driven by p53 activation as part program.