Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
Cell Stem Cell. 2022 Mar 3;29(3):449-459.e6. doi: 10.1016/j.stem.2022.01.014. Epub 2022 Feb 24.
The activation of the embryonic genome marks the first major wave of transcription in the developing organism. Zygotic genome activation (ZGA) in mouse 2-cell embryos and 8-cell embryos in humans is crucial for development. Here, we report the discovery of human 8-cell-like cells (8CLCs) among naive embryonic stem cells, which transcriptionally resemble the 8-cell human embryo. They express ZGA markers, including ZSCAN4 and LEUTX, and transposable elements, such as HERVL and MLT2A1. 8CLCs show reduced SOX2 levels and can be identified using TPRX1 and H3.Y marker proteins in vitro. Overexpression of the transcription factor DUX4 and spliceosome inhibition increase human ZGA-like transcription. Excitingly, the 8CLC markers TPRX1 and H3.Y are also expressed in ZGA-stage 8-cell human embryos and may thus be relevant in vivo. 8CLCs provide a unique opportunity to characterize human ZGA-like transcription and might provide critical insights into early events in embryogenesis in humans.
胚胎基因组的激活标志着发育生物体中首次主要的转录波。在小鼠 2 细胞胚胎和人类 8 细胞胚胎中，合子基因组激活（ZGA）对于发育至关重要。在这里，我们报告了在幼稚胚胎干细胞中发现了人类 8 细胞样细胞（8CLC），其转录上类似于 8 细胞人类胚胎。它们表达 ZGA 标记物，包括 ZSCAN4 和 LEUTX，以及转座元件，如 HERVL 和 MLT2A1。8CLC 显示 SOX2 水平降低，并且可以使用 TPRX1 和 H3.Y 标记蛋白在体外进行鉴定。转录因子 DUX4 的过表达和剪接体抑制增加了人类 ZGA 样转录。令人兴奋的是，8CLC 标记物 TPRX1 和 H3.Y 也在 ZGA 阶段的 8 细胞人类胚胎中表达，因此可能与体内相关。8CLC 为研究人类 ZGA 样转录提供了独特的机会，并可能为人类胚胎发生的早期事件提供关键见解。
