Transcriptome analyses of rhesus monkey pre-implantation embryos reveal a reduced capacity for DNA double strand break repair in primate oocytes and early embryos
- Xinyi Wang1,
- Denghui Liu2,
- Dajian He1,
- Shengbo Suo2,
- Xian Xia2,
- Xiechao He1,
- Jing-Dong Han2 and
- Ping Zheng1,3
- 1 Kunming Institute of Zoology, Chinese Academy of Sciences;
- 2 Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology
- ↵* Corresponding author; email: zhengp{at}mail.kiz.ac.cn
Abstract
Pre-implantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell fate commitment, most of which remain mechanistically unclear in primates. In addition, primates display a high rate of embryo wastage without any clear molecular basis. Understanding the factors involved in genome reprogramming and ZGA will help the generation of induced pluripotent stem cells with high efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution. Here, we have carried out time-series RNA-seq studies in single and pooled rhesus monkey oocytes and pre-implantation embryos at representative developmental stages. By comparing to human and mouse data, we found that the transcriptome dynamics of monkey oocytes and embryos were very similar to those of human, but very different from those of mouse. We identified several classes of maternal and zygotic genes, whose expression peaks were highly correlated with the time frames of genome reprogramming, ZGA and cell fate commitment, respectively. Importantly, comparison of the ZGA-related network modules among the three species revealed a looser surveillance of genomic instability in primate oocytes and embryos than in rodents, particularly in the pathways of DNA damage signaling and homology-directed DNA double strand break repair. This study highlights the importance of utilizing rhesus monkey to explore the molecular basis of genome reprogramming, ZGA, and genomic stability surveillance in human early embryogenesis, and provides important clues on how to improve the efficiency of homologous recombination-mediated gene editing in monkey transgenic technology.
- Received August 8, 2015.
- Accepted February 10, 2017.
- Published by Cold Spring Harbor Laboratory Press
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