英国威康桑格研究所Michael R. Stratton小组利用体细胞突变推断出人类发育的广泛系统发生。这一研究成果于2021年8月25日在线发表在国际学术期刊《自然》上。
研究人员利用511个激光捕获显微切片的全基因组测序，重建了三个成年个体正常组织的广泛系统发生。在系统发生的同一代中，重建的胚胎祖先往往对成年身体的贡献程度不同。这种不对称的程度因人而异，子代两个重建子细胞之间的比例从60:40到93:7不等。不对称性弥漫在随后的几代中，在同一个体的不同组织之间也会有所不同。系统发生解决了组织的空间胚胎模式化问题，揭示了成年结肠上皮细胞中平均有301个隐窝的连续斑块，这些隐窝来自于最近的胚胎细胞，在大脑发育中也有空间效应。
利用另外10名男性的数据，研究人员调查了体细胞和生殖细胞之间的发育分裂，并揭示了对原始生殖细胞的胚胎外贡献。这项研究表明，尽管达到了相同的最终组织模式，但早期瓶颈和谱系建立导致了个体内部和个体之间胚胎模式的巨大差异。
据悉，从胚胎开始，人体的所有细胞都不断获得突变。不同细胞之间共享的突变意味着有一个共同的祖先，因此是自然发生的谱系追踪标记。
附：英文原文
Title: Extensive phylogenies of human development inferred from somatic mutations
Author: Coorens, Tim H. H., Moore, Luiza, Robinson, Philip S., Sanghvi, Rashesh, Christopher, Joseph, Hewinson, James, Przybilla, Moritz J., Lawson, Andrew R. J., Spencer Chapman, Michael, Cagan, Alex, Oliver, Thomas R. W., Neville, Matthew D. C., Hooks, Yvette, Noorani, Ayesha, Mitchell, Thomas J., Fitzgerald, Rebecca C., Campbell, Peter J., Martincorena, Iigo, Rahbari, Raheleh, Stratton, Michael R.
Issue&Volume: 2021-08-25
Abstract: Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing1,2. Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals.
DOI: 10.1038/s41586-021-03790-y
Source: https://www.nature.com/articles/s41586-021-03790-y
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
