Human embryos harbor complex mosaicism with broad presence of aneuploid cells during early development.

IF 13 1区生物学 Q1 CELL BIOLOGY

Cell Discovery Pub Date : 2024-09-24 DOI:10.1038/s41421-024-00719-3

Fan Zhai, Siming Kong, Shi Song, Qianying Guo, Ling Ding, Jiaqi Zhang, Nan Wang, Ying Kuo, Shuo Guan, Peng Yuan, Liying Yan, Zhiqiang Yan, Jie Qiao

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引用次数: 0

Abstract

Pre-implantation genetic testing for aneuploidy (PGT-A) is used in approximately half of in vitro fertilization cycles. Given the limited understanding of the genetics of human embryos, the current use of PGT-A is based on biologically uncertain assumptions and unvalidated guidelines, leading to the possibility of disposing of embryos with pregnancy potential. We isolated and sequenced all single cells (1133) from in vitro cultured 20 human blastocysts. We found that all blastocysts exhibited mosaicism with mitotic-induced aneuploid cells and showed an ~25% aneuploidy rate per embryo. Moreover, 70% (14/20) of blastocysts contained 'chromosome-complementary' cells, suggesting genetic mosaicism is underestimated in routine PGT-A. Additionally, the analysis of 20,945 single cells from day 8-14 embryos (in vitro cultured) and embryonic/fetal organs showed that 97% of the analyzed embryos/organs were mosaic. Over 96% of their aneuploid cells harbored ≤ 2 chromosome errors. Our findings have revealed a high prevalence of mosaicism in human embryos.

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人类胚胎在早期发育过程中存在复杂的嵌合现象，非整倍体细胞广泛存在。

约有一半的体外受精周期使用植入前非整倍体基因检测（PGT-A）。由于对人类胚胎遗传学的了解有限，目前 PGT-A 的使用是基于生物学上不确定的假设和未经验证的指导原则，从而可能导致具有妊娠潜能的胚胎被弃置。我们对体外培养的 20 个人类囊胚的所有单细胞（1133 个）进行了分离和测序。我们发现，所有囊胚都表现出与有丝分裂诱导的非整倍体细胞嵌合，每个胚胎的非整倍体率约为 25%。此外，70%（14/20）的囊胚含有 "染色体互补 "细胞，这表明在常规 PGT-A 中基因嵌合被低估了。此外，对来自第 8-14 天胚胎（体外培养）和胚胎/胎儿器官的 20,945 个单细胞进行的分析表明，97% 的受分析胚胎/器官是镶嵌的。96%以上的非整倍体细胞含有≤2条染色体错误。我们的研究结果表明，人类胚胎中镶嵌现象非常普遍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

24.20

自引率

0.60%

发文量

120

审稿时长

20 weeks

期刊介绍： Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.