Teixeira Vitor H, Nadarajan Parthiban, Graham Trevor A, Pipinikas Christodoulos P, Brown James M, Falzon Mary, Nye Emma, Poulsom Richard, Lawrence David, Wright Nicholas A, McDonald Stuart, Giangreco Adam, Simons Benjamin D, Janes Sam M
Lungs for Living Research Centre, UCL Respiratory , University College London , London , United Kingdom.
Elife. 2013 Oct 22;2:e00966. doi: 10.7554/eLife.00966.
Lineage tracing approaches have provided new insights into the cellular mechanisms that support tissue homeostasis in mice. However, the relevance of these discoveries to human epithelial homeostasis and its alterations in disease is unknown. By developing a novel quantitative approach for the analysis of somatic mitochondrial mutations that are accumulated over time, we demonstrate that the human upper airway epithelium is maintained by an equipotent basal progenitor cell population, in which the chance loss of cells due to lineage commitment is perfectly compensated by the duplication of neighbours, leading to "neutral drift" of the clone population. Further, we show that this process is accelerated in the airways of smokers, leading to intensified clonal consolidation and providing a background for tumorigenesis. This study provides a benchmark to show how somatic mutations provide quantitative information on homeostatic growth in human tissues, and a platform to explore factors leading to dysregulation and disease. DOI:http://dx.doi.org/10.7554/eLife.00966.001.
谱系追踪方法为支持小鼠组织稳态的细胞机制提供了新的见解。然而，这些发现与人类上皮稳态及其在疾病中的改变之间的相关性尚不清楚。通过开发一种用于分析随时间积累的体细胞线粒体突变的新型定量方法，我们证明人类上呼吸道上皮由一个等效的基底祖细胞群体维持，在这个群体中，由于谱系分化导致的细胞随机丢失通过相邻细胞的复制得到完美补偿，从而导致克隆群体的“中性漂移”。此外，我们表明这个过程在吸烟者的气道中加速，导致克隆合并加剧，并为肿瘤发生提供了背景。这项研究提供了一个基准，以展示体细胞突变如何提供关于人类组织稳态生长的定量信息，以及一个探索导致失调和疾病的因素的平台。DOI:http://dx.doi.org/10.7554/eLife.00966.001
