体细胞突变揭示人类胚胎发育的标志，这一成果由美国波士顿儿童医院Christopher A. Walsh和哈佛医学院Peter J. Park课题组合作取得。2021年3月19日出版的《科学》杂志发表了这一最新研究成果。

研究人员对来自三个个体的多组织进行了深度（250×）全基因组测序，以鉴定数百种体细胞的单核苷酸突变体（sSNV）。使用这些变体作为单个细胞的“内源条形码”，研究人员重构了早期胚胎细胞分裂。

针对不同器官（约25,000×）和1000多个皮质单细胞中的克隆sSNV靶向测序，以及用约100,000个皮质单细胞转座酶以及染色质测序的单核RNA测序和单核测定，研究人员证明不对称早期祖细胞对胚外组织、不同滋养层和器官的贡献。

该研究数据表明，在大约170个细胞和大约50至100个前脑祖细胞库中开启了原肠胚形成。因此，镶嵌突变以非常高的分辨率提供了人类胚胎发育的永久记录。

据了解，尽管细胞谱系信息是了解组织发育的基础，但几乎没有直接可用于人类的谱系信息。

附：英文原文

Title: Landmarks of human embryonic development inscribed in somatic mutations

Author: Sara Bizzotto, Yanmei Dou, Javier Ganz, Ryan N. Doan, Minseok Kwon, Craig L. Bohrson, Sonia N. Kim, Taejeong Bae, Alexej Abyzov, NIMH Brain Somatic Mosaicism Network, Peter J. Park, Christopher A. Walsh

Issue&Volume: 2021/03/19

Abstract: Although cell lineage information is fundamental to understanding organismal development, very little direct information is available for humans. We performed high-depth (250×) whole-genome sequencing of multiple tissues from three individuals to identify hundreds of somatic single-nucleotide variants (sSNVs). Using these variants as “endogenous barcodes” in single cells, we reconstructed early embryonic cell divisions. Targeted sequencing of clonal sSNVs in different organs (about 25,000×) and in more than 1000 cortical single cells, as well as single-nucleus RNA sequencing and single-nucleus assay for transposase-accessible chromatin sequencing of ~100,000 cortical single cells, demonstrated asymmetric contributions of early progenitors to extraembryonic tissues, distinct germ layers, and organs. Our data suggest onset of gastrulation at an effective progenitor pool of about 170 cells and about 50 to 100 founders for the forebrain. Thus, mosaic mutations provide a permanent record of human embryonic development at very high resolution.

DOI: 10.1126/science.abe1544

Source: https://science.sciencemag.org/content/371/6535/1249