Nature：人胎盘基因组学研究新进展
- ①胎盘可表现出与胎儿不同的染色体畸变，这种遗传分离基础被称之为“胎盘镶嵌”，原因未知；
- ②本研究通过对86个胎盘组织样品的全基因组测序，发现每块胎盘样本中都代表了一个在遗传上截然不同的克隆；
- ③同时，在突变负担和突变印迹方面表现出于儿童期癌症类似的基因组格局；
- ④在某些情况下，胎盘谱系和源自内部细胞团的谱系是完全分离的；
- ⑤该研究揭示了胎盘组织中的广泛的突变，并提示镶嵌现象是胎盘发育的典型特征；
主编推荐语
胎盘基因组改变可能是胎盘功能障碍的发病机制，这是所谓胎盘功能障碍（包括先兆子痫，胎儿生长限制和死产）的关键决定因素。本研究发现，基因组改变通常在胎盘内并不均匀分布，这可能解释了在存在镶嵌的情况下观察到的那些妊娠结果的可变性。
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Inherent mosaicism and extensive mutation of human placentas
人类胎盘的固有镶嵌现象和广泛突变
10.1038/s41586-021-03345-1
2021-03-10, Article
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Abstract:
Placentas can exhibit chromosomal aberrations that are absent from the fetus1. The basis of this genetic segregation, which is known as confned 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 fndings reveal extensive mutagenesis in placental tissues and suggest that mosaicism is a typical feature of placental development.
First Authors:
Tim H H Coorens,Thomas R W Oliver
Correspondence Authors:
D Stephen Charnock-Jones,Gordon C S Smith,Sam Behjati
All Authors:
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
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