A program of successive gene expression in mouse one-cell embryos
A program of successive gene expression in mouse one-cell embryos
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DOI：
10.1016/j.celrep.2023.112023
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发表时间：
2023-01-31
期刊：
影响因子：
8.8
通讯作者：
Perry, Anthony C. F.
中科院分区：
文献类型：
--
作者：
Asami, Maki;Lam, Brian Y. H.;Perry, Anthony C. F.
在受精结合的那一刻，精子和卵母细胞的转录是沉默的。随后的胚胎转录开始（胚胎基因组激活[EGA]）对于发育至关重要，但其时间和概况在任何脊椎动物物种中仍然难以捉摸。我们在这里通过精确同步的小鼠单细胞胚胎的高分辨率单细胞 RNA 测序来剖析 EGA 期间的转录。这揭示了受精后 4 小时内启动的胚胎基因表达程序（立即 EGA [iEGA]）。 iEGA 期间的表达产生规范剪接的转录本，基本上来自母体基因组，并且在双细胞阶段大部分被下调。转录基因预测与癌症相关的转录因子 (TF) 的调节，包括 c-Myc。阻断 c-Myc 或其他预测的调节 TF 活性会破坏 iEGA 并诱导急性发育停滞。这些发现阐明了调节哺乳动物发育开始的细胞内机制，并为癌症研究带来了希望。
At the moment of union in fertilization, sperm and oocyte are transcriptionally silent. The ensuing onset of embryonic transcription (embryonic genome activation [EGA]) is critical for development, yet its timing and profile remain elusive in any vertebrate species. We here dissect transcription during EGA by high -res-olution single-cell RNA sequencing of precisely synchronized mouse one-cell embryos. This reveals a pro-gram of embryonic gene expression (immediate EGA [iEGA]) initiating within 4 h of fertilization. Expression during iEGA produces canonically spliced transcripts, occurs substantially from the maternal genome, and is mostly downregulated at the two-cell stage. Transcribed genes predict regulation by transcription factors (TFs) associated with cancer, including c-Myc. Blocking c-Myc or other predicted regulatory TF activities dis-rupts iEGA and induces acute developmental arrest. These findings illuminate intracellular mechanisms that regulate the onset of mammalian development and hold promise for the study of cancer.