Recapitulating early human development with 8C-like cells
Recapitulating early human development with 8C-like cells
复制标题
用 8C 样细胞重现早期人类发育
DOI：
10.1016/j.celrep.2022.110994
复制
发表时间：
2022-06-21
期刊：
影响因子：
8.8
通讯作者：
Wang, Jichang
中科院分区：
文献类型：
--
作者：
Yu, Xiu;Liang, Shiqi;Wang, Jichang
在人类胚胎中，主要合子基因组激活（ZGA）起始于八细胞（8C）阶段。ZGA异常导致发育缺陷，甚至导致人类囊胚形成或植入失败。模拟人类8C卵裂球的体外细胞模型对于理解人类早期发育过程中调节关键生物学事件的机制将是非常宝贵的。使用非典型的启动子的LEUTX，pupletin调节人类ZGA，我们开发了一个8C：：mCherry报告，它特异性地标志着8C状态，以分离罕见的8C样细胞（8CLC）从人类植入前外胚层样干细胞。8CLC表达一组人ZGA基因，并具有类似于人8C胚胎的独特转录组。使用8C：：mCherry报告基因，我们进一步优化了基于化学的培养条件以增加和维持8CLC群体。在功能上，8CLC可以自组织形成胚泡样结构。8CLC的发现和维持为重现早期人类发育提供了机会。
In human embryos, major zygotic genome activation (ZGA) initiates at the eight-cell (8C) stage. Abnormal ZGA leads to developmental defects and even contributes to the failure of human blastocyst formation or implantation. An in vitro cell model mimicking human 8C blastomeres would be invaluable to understanding the mechanisms regulating key biological events during early human development. Using the non-canonical promoter of LEUTX that putatively regulates human ZGA, we developed an 8C::mCherry reporter, which specifically marks the 8C state, to isolate rare 8C-like cells (8CLCs) from human preimplantation epiblast-like stem cells. The 8CLCs express a panel of human ZGA genes and have a unique transcriptome resembling that of the human 8C embryo. Using the 8C::mCherry reporter, we further optimize the chemical-based culture condition to increase and maintain the 8CLC population. Functionally, 8CLCs can self-organize to form blastocyst-like structures. The discovery and maintenance of 8CLCs provide an opportunity to recapitulate early human development.