美国加州大学圣迭戈分校Tien Peng研究小组发现，基底膜上的哨兵p16^INK4a+细胞在肺部形成一个修复性微环境。相关论文发表在2022年10月14日出版的《科学》杂志上。

研究人员设计了一个p16^INK4a的超灵敏报告器，这是一个细胞衰老的生物标志物。这个报告器检测到具有某些衰老特征的p16^INK4a表达的成纤维细胞，这些成纤维细胞出生后不久就出现在肺部上皮干细胞附近的基底膜上。此外，这些p16^INK4a+成纤维细胞感知组织炎症的能力增强，并通过其增加的分泌能力作出反应，促进上皮细胞的再生。

此外，p16^INK4a的表达对成纤维细胞增强上皮再生是需要的。这项研究强调了p16^INK4a+成纤维细胞作为干细胞微环境中的组织驻留哨兵的作用，它们监测屏障的完整性，并迅速对炎症作出反应，促进组织再生。

附：英文原文

Title: Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung

Author: 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

Issue&Volume: 2022-10-14

Abstract: We engineered an ultrasensitive reporter of p16INK4a, a biomarker of cellular senescence. Our reporter detected p16INK4a-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 p16INK4a+ fibroblasts had enhanced capacity to sense tissue inflammation and respond through their increased secretory capacity to promote epithelial regeneration. In addition, p16INK4a expression was required in fibroblasts to enhance epithelial regeneration. This study highlights a role for p16INK4a+ fibroblasts as tissue-resident sentinels in the stem cell niche that monitor barrier integrity and rapidly respond to inflammation to promote tissue regeneration.

DOI: abf3326

Source: https://www.science.org/doi/10.1126/science.abf3326