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

Autor: Nabora S. Reyes, Maria Krasilnikov, Nancy C. Allen, Jin Young Lee, Ben Hyams, Minqi Zhou, Supriya Ravishankar, Monica Cassandras, Chaoqun Wang, Imran Khan, Peri Matatia, Yoshikazu Johmura, Ari Molofsky, Michael Matthay, Makoto Nakanishi, Dean Sheppard, Judith Campisi, Tien Peng
Rok vydání: 2022
Předmět:
Zdroj: Science. 378:192-201
ISSN: 1095-9203
0036-8075
DOI: 10.1126/science.abf3326
Popis: We engineered an ultrasensitive reporter of p16 INK4a , a biomarker of cellular senescence. Our reporter detected p16 INK4a -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 p16 INK4a+ fibroblasts had enhanced capacity to sense tissue inflammation and respond through their increased secretory capacity to promote epithelial regeneration. In addition, p16 INK4a expression was required in fibroblasts to enhance epithelial regeneration. This study highlights a role for p16 INK4a+ fibroblasts as tissue-resident sentinels in the stem cell niche that monitor barrier integrity and rapidly respond to inflammation to promote tissue regeneration.
Databáze: OpenAIRE
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