Single-cell DNA methylome sequencing of human preimplantation embryos
Single-cell DNA methylome sequencing of human preimplantation embryos
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人类植入前胚胎的单细胞 DNA 甲基化组测序
DOI：
10.1038/s41588-017-0007-6
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发表时间：
2018-01-01
期刊：
影响因子：
30.8
通讯作者：
Tang, Fuchou
中科院分区：
文献类型：
--
作者：
Zhu, Ping;Guo, Hongshan;Tang, Fuchou
DNA 甲基化是哺乳动物胚胎发育过程中表观遗传调控的关键层1-3。尽管早期人类胚胎的 DNA 甲基化组已被分析4-6，但迄今为止，一些关键特征尚未得到解决。在这里，我们对人类植入前胚胎进行了单细胞 DNA 甲基化测序，发现数以万计的基因组位点表现出从头 DNA 甲基化。这一发现表明，植入前发育过程中全基因组 DNA 甲基化重编程是强整体去甲基化和剧烈集中再甲基化之间的动态平衡。此外，父本基因组的去甲基化比母本基因组的去甲基化更快、更彻底。从双细胞到植入后阶段，父本基因组的甲基化始终低于母本基因组的甲基化。我们还表明，早期卵裂球的遗传谱系可以通过 DNA 甲基化分析来追踪。我们的工作为破译早期人类胚胎 DNA 甲基化重编程的秘密铺平了道路。
DNA methylation is a crucial layer of epigenetic regulation during mammalian embryonic development1-3. Although the DNA methylome of early human embryos has been analyzed4-6, some of the key features have not been addressed thus far. Here we performed single-cell DNA methylome sequencing for human preimplantation embryos and found that tens of thousands of genomic loci exhibited de novo DNA methylation. This finding indicates that genome-wide DNA methylation reprogramming during preimplantation development is a dynamic balance between strong global demethylation and drastic focused remethylation. Furthermore, demethylation of the paternal genome is much faster and thorough than that of the maternal genome. From the two-cell to the postimplantation stage, methylation of the paternal genome is consistently lower than that of the maternal genome. We also show that the genetic lineage of early blastomeres can be traced by DNA methylation analysis. Our work paves the way for deciphering the secrets of DNA methylation reprogramming in early human embryos.