Sentinel p16 INK4a+ cells in the basement membrane form a reparative niche in the lung

• Published in: Science (American Association for the Advancement of Science) Vol. 378; no. 6616; pp. 192 - 201
• Main Authors: Reyes, Nabora S, Krasilnikov, Maria, Allen, Nancy C, Lee, Jin Young, Hyams, Ben, Zhou, Minqi, Ravishankar, Supriya, Cassandras, Monica, Wang, Chaoqun, Khan, Imran, Matatia, Peri, Johmura, Yoshikazu, Molofsky, Ari, Matthay, Michael, Nakanishi, Makoto, Sheppard, Dean, Campisi, Judith, Peng, Tien
• Format: Journal Article
• Language: English
• Published: United States 14-10-2022
• Subjects: Basement Membrane - cytology; Basement Membrane - physiology; Biomarkers - metabolism; Cellular Senescence - genetics; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Epithelial Cells - physiology; Fibroblasts - metabolism; Genes, Reporter; Humans; Inflammation - metabolism; Lung - pathology; Lung - physiology; Regeneration; Stem Cell Niche - physiology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abf3326

We engineered an ultrasensitive reporter of
, a biomarker of cellular senescence. Our reporter detected
-expressing fibroblasts with certain senescent characteristics that appeared shortly after birth in the basement membrane adjacent to epithelial stem cells in the lung. Furthermore, these
fibroblasts had enhanced capacity to sense tissue inflammation and respond through their increased secretory capacity to promote epithelial regeneration. In addition,
expression was required in fibroblasts to enhance epithelial regeneration. This study highlights a role for
fibroblasts as tissue-resident sentinels in the stem cell niche that monitor barrier integrity and rapidly respond to inflammation to promote tissue regeneration.