Department of Medicine, Pulmonary and Critical Care Division, University of California San Francisco, San Francisco, CA, USA.
Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Science. 2022 Oct 14;378(6616):192-201. doi: 10.1126/science.abf3326. Epub 2022 Oct 13.
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.
我们设计了一种超灵敏的细胞衰老生物标志物 的报告器。我们的报告器检测到表达 - 的成纤维细胞具有某些衰老特征,这些特征在出生后不久就出现在肺上皮干细胞附近的基底膜中。此外,这些成纤维细胞具有增强的感知组织炎症的能力,并通过增加分泌能力来促进上皮细胞再生。此外,成纤维细胞中表达 对于增强上皮细胞再生是必需的。这项研究强调了 成纤维细胞作为组织驻留的哨兵在干细胞龛中的作用,它们监测屏障完整性,并迅速响应炎症以促进组织再生。