Inferring the choreography of parental genomes during fertilization from ultralarge-scale whole-transcriptome analysis.

Inferring the choreography of parental genomes during fertilization from ultralarge-scale whole-transcriptome analysis.
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DOI:
10.1101/gad.227926.113
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发表时间:
2013-12-15
影响因子:
10.5
通讯作者:
Shirahige K
Shirahige K
中科院分区:
生物学1区
文献类型:
--
作者:
Park SJ;Komata M;Inoue F;Yamada K;Nakai K;Ohsugi M;Shirahige K

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哺乳动物受精后亲本基因组协调的机制仍然难以捉摸,因为难以制备大量高质量的植入前细胞。在这里,Park等人收集了前所未有数量的小鼠卵母细胞,并建立了四个早期胚胎阶段和孤雌发育的详细转录谱。生物信息学分析确定了一个独特的基因调控网络激活受精后的胚胎相比,单性生殖。这种早期小鼠胚胎的大规模概况为发育生物学和干细胞研究提供了宝贵的资源。受精通过使用配子衍生的细胞因子和激活基因组调控程序来精确地编排亲本基因组。然而,由于制备大量高质量的植入前细胞的技术困难,该机制仍然难以捉摸。在这里,我们收集了>14 × 104个高质量的小鼠中期II卵母细胞,并使用这些卵母细胞建立了四个早期胚胎阶段和孤雌发育的详细转录谱。通过将这些图谱与其他公共资源相结合,我们发现了基因沉默似乎部分由非编码RNA介导的证据,这是受精后发育的先决条件。值得注意的是,我们确定了817个基因的差异表达受精后的胚胎与单性生殖。这些基因的调控明显不同于那些在单性生殖体中表达的基因,这表明在第一次细胞分裂之前特定转录因子的功能特化。我们确定了五个转录因子,可能是必要的发育进程:Foxd 1,Nkx 2 -5,Sox 18,Myod 1和Runx 1。我们对早期小鼠胚胎的大规模全转录组图谱为发育生物学和干细胞研究提供了一种新的有价值的资源。该数据库可在http://dbtmee.hgc.jp上查阅。
The mechanisms underlying parental genome coordination upon mammalian fertilization remain elusive due to difficulties in preparing large numbers of high-quality preimplantation cells. Here, Park et al. collect an unprecedented number of mouse oocytes and establish detailed transcriptional profiles for four early embryonic stages and parthenogenetic development. Bioinformatic analysis identifies a distinctive gene regulatory network activated in embryos after fertilization compared with parthenotes. This large-scale profile of early mouse embryos yields a valuable resource for developmental biology and stem cell research. Fertilization precisely choreographs parental genomes by using gamete-derived cellular factors and activating genome regulatory programs. However, the mechanism remains elusive owing to the technical difficulties of preparing large numbers of high-quality preimplantation cells. Here, we collected >14 × 104 high-quality mouse metaphase II oocytes and used these to establish detailed transcriptional profiles for four early embryo stages and parthenogenetic development. By combining these profiles with other public resources, we found evidence that gene silencing appeared to be mediated in part by noncoding RNAs and that this was a prerequisite for post-fertilization development. Notably, we identified 817 genes that were differentially expressed in embryos after fertilization compared with parthenotes. The regulation of these genes was distinctly different from those expressed in parthenotes, suggesting functional specialization of particular transcription factors prior to first cell cleavage. We identified five transcription factors that were potentially necessary for developmental progression: Foxd1, Nkx2-5, Sox18, Myod1, and Runx1. Our very large-scale whole-transcriptome profile of early mouse embryos yielded a novel and valuable resource for studies in developmental biology and stem cell research. The database is available at http://dbtmee.hgc.jp.
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