8C-like cells capture the human zygotic genome activation program in vitro

被引：98

作者：

Taubenschmid-Stowers, Jasmin ^{[1
]}

Rostovskaya, Maria ^{[1
]}

Santos, Fatima ^{[1
,2
]}

Ljung, Sebastian ^{[1
]}

Argelaguet, Ricard ^{[1
]}

Krueger, Felix ^{[1
]}

Nichols, Jennifer ^{[2
,3
,4
]}

Reik, Wolf ^{[1
,2
,5
]}

机构：

[1] Babraham Inst, Epigenet Programme, Cambridge CB22 3AT, England

[2] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England

[3] Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge CB2 0AW, England

[4] Univ Cambridge, Dept Physiol, Cambridge CB2 3EL, England

[5] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

来源：

CELL STEM CELL | 2022年 / 29卷 / 03期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

PLURIPOTENT STEM-CELLS; HUMAN PREIMPLANTATION EMBRYOS; GENE-EXPRESSION; MUERV-L; NAIVE; TRANSCRIPTION; STATE; DUX4; ZSCAN4;

D O I：

10.1016/j.stem.2022.01.014

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：449 / +

页数：18

共 65 条

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