Department of Genetics, Albert Einstein College of Medicine, New York, NY 10461, USA; Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Department of Genetics, Albert Einstein College of Medicine, New York, NY 10461, USA.
Cell. 2020 Jul 9;182(1):12-23. doi: 10.1016/j.cell.2020.06.024.
Age-related accumulation of postzygotic DNA mutations results in tissue genetic heterogeneity known as somatic mosaicism. Although implicated in aging as early as the 1950s, somatic mutations in normal tissue have been difficult to study because of their low allele fractions. With the recent emergence of cost-effective high-throughput sequencing down to the single-cell level, enormous progress has been made in our capability to quantitatively analyze somatic mutations in human tissue in relation to aging and disease. Here we first review how recent technological progress has opened up this field, providing the first broad sets of quantitative information on somatic mutations in vivo necessary to gain insight into their possible causal role in human aging and disease. We then propose three major mechanisms that can lead from accumulated de novo mutations across tissues to cell functional loss and human disease.
随着近年来成本效益高的高通量测序技术的出现，单细胞水平的测序技术已达到实用水平，我们在定量分析人类组织中的体细胞突变与衰老和疾病的关系方面取得了巨大进展。在这里，我们首先回顾了最近的技术进步如何开辟了这一领域，提供了关于体内体细胞突变的第一批广泛的定量信息，这些信息对于深入了解它们在人类衰老和疾病中的可能因果作用是必要的。然后，我们提出了三个主要机制，这些机制可以从跨组织积累的新生突变导致细胞功能丧失和人类疾病。
