Figure 1.

Aberrant epithelial cell senescence is a hallmark of fibrotic lung disease. RNA ISH was performed with a probe against transcript variant 1 of the human Cdkn2a gene locus, specifically detecting the p16^ink4a-coding transcript, on histological slides from four human donors with end-stage interstitial lung disease or idiopathic pulmonary fibrosis and one human donor without lung disease. Demographic information is noted in Supplementary Table 1. Example red ISH puncta representing p16^ink4a transcripts are identified with an arrow, and areas of p16^ink4a-negative fibroblastic foci are marked with an asterisk. Expression of p16^ink4a mRNA expression across cell types per donor using a semi-quantitative 0–3 scale is shown in the associated table. (A) No Cdkn2a mRNA is observed in bronchiolar epithelium of normal lung, (B–F) Cdkn2a mRNA is present in the aberrant epithelium overlying fibroblastic foci (asterisk) and in the aberrant epithelium lining honeycomb cysts in diseased lung.