美国耶鲁大学Flora M. Vaccarino和美国梅奥诊所个体化医学中心Alexej Abyzov团队合作取得一项新突破。他们研究了在活体个体中细胞谱系树的早期发育不对称性。这一研究成果于2021年3月18日发表在《科学》杂志上。

他们利用细胞克隆技术分析了两个活体个体和一个死后人标本中的胚胎细胞谱系。 在10个重建的合子后分裂中，没有一个导致子代谱系对组织的平衡贡献。在两个活体个体中，从第一次卵裂开始的两个谱系中的一个在整个组织中占优势，在血液中的频率为90％。

他们表明DNA修复的效率有助于沿袭不平衡。死后脑中谱系的分配与前后轴相关，将谱系历史与胚胎中的细胞命运选择相关联。他们建立了一个用于定义任何活体个体中细胞谱系的微创框架，这为研究它们在健康和疾病中的相关性铺平了道路。

据介绍，镶嵌突变可用于追踪人类的细胞谱系。

附：英文原文

Title: Early developmental asymmetries in cell lineage trees in living individuals

Author: Liana Fasching, Yeongjun Jang, Simone Tomasi, Jeremy Schreiner, Livia Tomasini, Melanie V. Brady, Taejeong Bae, Vivekananda Sarangi, Nikolaos Vasmatzis, Yifan Wang, Anna Szekely, Thomas V. Fernandez, James F. Leckman, Alexej Abyzov, Flora M. Vaccarino

Issue&Volume: 2021/03/19

Abstract: Mosaic mutations can be used to track cell lineages in humans. We used cell cloning to analyze embryonic cell lineages in two living individuals and a postmortem human specimen. Of 10 reconstructed postzygotic divisions, none resulted in balanced contributions of daughter lineages to tissues. In both living individuals, one of two lineages from the first cleavage was dominant across tissues, with 90% frequency in blood. We propose that the efficiency of DNA repair contributes to lineage imbalance. Allocation of lineages in postmortem brain correlated with anterior-posterior axis, associating lineage history with cell fate choices in embryos. We establish a minimally invasive framework for defining cell lineages in any living individual, which paves the way for studying their relevance in health and disease.

DOI: 10.1126/science.abe0981

Source: https://science.sciencemag.org/content/371/6535/1245