Sentinel p16 INK4a+ cells in the basement membrane form a reparative niche in the lung.
Nabora S ReyesMaria KrasilnikovNancy C AllenJin Young LeeBen HyamsMinqi ZhouSupriya RavishankarMonica CassandrasChaoqun WangImran S KhanPeri R MatatiaYoshikazu JohmuraAri B MolofskyMichael A MatthayMakoto NakanishiDean SheppardJudith CampisiTien PengPublished in: Science (New York, N.Y.) (2022)
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.
Keyphrases
- stem cells
- extracellular matrix
- oxidative stress
- cell therapy
- induced apoptosis
- poor prognosis
- gold nanoparticles
- dna damage
- patient safety
- endothelial cells
- mesenchymal stem cells
- cell cycle arrest
- bone marrow
- endoplasmic reticulum stress
- high resolution
- stress induced
- quality improvement
- preterm birth
- simultaneous determination