英国威康桑格研究所Sam Behjati等研究人员合作发现，人类胎盘存在遗传镶嵌和广泛突变。该项研究成果于2021年3月10日在线发表在《自然》杂志上。
使用了86个大块的胎盘样品（中位重量为28 mg）和106个胎盘组织显微切割的全基因组测序，研究人员揭示了从体细胞突变中重建的人类胎盘细胞的系统发育。研究人员发现，每个大块的胎盘样本都代表了一个在遗传上截然不同的克隆扩增，并且在突变负担和突变印记方面表现出与儿童期癌症类似的基因组格局。与迄今为止研究的任何其他健康人体组织不同，胎盘基因组通常包含拷贝数变化。研究人员重建了同一次怀孕的组织之间的系统发育关系，这揭示了发育瓶颈通过将滋养表皮谱系与源自内部细胞团的谱系分离而遗传隔离了胎盘组织。
值得注意的是，在某些情况下，胎盘谱系和源自内部细胞团的谱系完全分离。这种早期胚胎瓶颈可能使合子的非整倍性正常化。研究人员在马赛克三合子拯救的情况下观察到了直接的证据。这项发现揭示了胎盘组织中的广泛诱变，并提示镶嵌是胎盘发育的典型特征。
据了解，胎盘可表现出胎儿中没有的染色体畸变。这种遗传分隔（被称为局限性胎盘镶嵌）的基础仍是未知的。
附：英文原文
Title: Inherent mosaicism and extensive mutation of human placentas
Author: Tim H. H. Coorens, Thomas R. W. Oliver, Rashesh Sanghvi, Ulla Sovio, Emma Cook, Roser Vento-Tormo, Muzlifah Haniffa, Matthew D. Young, Raheleh Rahbari, Neil Sebire, Peter J. Campbell, D. Stephen Charnock-Jones, Gordon C. S. Smith, Sam Behjati
Issue&Volume: 2021-03-10
Abstract: Placentas can exhibit chromosomal aberrations that are absent from the fetus1. The basis of this genetic segregation, which is known as confined placental mosaicism, remains unknown. Here we investigated the phylogeny of human placental cells as reconstructed from somatic mutations, using whole-genome sequencing of 86 bulk placental samples (with a median weight of 28 mg) and of 106 microdissections of placental tissue. We found that every bulk placental sample represents a clonal expansion that is genetically distinct, and exhibits a genomic landscape akin to that of childhood cancer in terms of mutation burden and mutational imprints. To our knowledge, unlike any other healthy human tissue studied so far, the placental genomes often contained changes in copy number. We reconstructed phylogenetic relationships between tissues from the same pregnancy, which revealed that developmental bottlenecks genetically isolate placental tissues by separating trophectodermal lineages from lineages derived from the inner cell mass. Notably, there were some cases with full segregation—within a few cell divisions of the zygote—of placental lineages and lineages derived from the inner cell mass. Such early embryonic bottlenecks may enable the normalization of zygotic aneuploidy. We observed direct evidence for this in a case of mosaic trisomic rescue. Our findings reveal extensive mutagenesis in placental tissues and suggest that mosaicism is a typical feature of placental development.
DOI: 10.1038/s41586-021-03345-1
Source: https://www.nature.com/articles/s41586-021-03345-1
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
