小柯机器人

美国阿尔伯特·爱因斯坦医学院Jan Vijg，Simon D. Spivack和Zhenqiu Huang共同合作取得重要进展。他们报道了与衰老和吸烟相关的人支气管上皮细胞体细胞突变的单细胞分析。相关论文2022年4月11日在线发表于《自然—遗传学》杂志上。

在这里，研究人员对33名的参与者(年龄：11岁~86岁；吸烟史：0包/年~116包/年）进行近端支气管基底细胞的单细胞全基因组测序。他们发现不吸烟者的单核苷酸变异和小插入及缺失的频率随着实际年龄的增长而增加，而吸烟者的突变频率显着升高。当与吸烟量（包/年）作图时，在吸烟量23（包/年）范围内，突变与随癌症风险呈线性相关，随着癌症风险的增加而增多，超过23（包/年）吸烟量之后没有观察到突变频率的进一步增加，这表明个体选择了避免突变。已知的肺癌定义的突变特征与年龄和吸烟都有追踪。没有观察到肺癌驱动基因中体细胞突变的显著富集。

据介绍，虽然吸烟者患肺癌的风险与吸烟剂量有关，但尚不清楚这种风险的增加是否反映了正常肺细胞中体细胞突变积累率的增加。

附：英文原文

Title: Single-cell analysis of somatic mutations in human bronchial epithelial cells in relation to aging and smoking

Author: Huang, Zhenqiu, Sun, Shixiang, Lee, Moonsook, Maslov, Alexander Y., Shi, Miao, Waldman, Spencer, Marsh, Ava, Siddiqui, Taha, Dong, Xiao, Peter, Yakov, Sadoughi, Ali, Shah, Chirag, Ye, Kenny, Spivack, Simon D., Vijg, Jan

Issue&Volume: 2022-04-11

Abstract: Although lung cancer risk among smokers is dependent on smoking dose, it remains unknown if this increased risk reflects an increased rate of somatic mutation accumulation in normal lung cells. Here, we applied single-cell whole-genome sequencing of proximal bronchial basal cells from 33 participants aged between 11 and 86 years with smoking histories varying from never-smoking to 116 pack-years. We found an increase in the frequency of single-nucleotide variants and small insertions and deletions with chronological age in never-smokers, with mutation frequencies significantly elevated among smokers. When plotted against smoking pack-years, mutations followed the linear increase in cancer risk until about 23 pack-years, after which no further increase in mutation frequency was observed, pointing toward individual selection for mutation avoidance. Known lung cancer-defined mutation signatures tracked with both age and smoking. No significant enrichment for somatic mutations in lung cancer driver genes was observed. Single-cell whole-genome sequencing of proximal bronchial basal cells shows that somatic mutations accumulate with age and at a higher level in smokers compared to never-smokers. Mutation frequencies increased with smoking dose but then plateaued, suggesting intrinsic mechanisms to limit mutation burden.

DOI: 10.1038/s41588-022-01035-w

Source: https://www.nature.com/articles/s41588-022-01035-w

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex