F1 Interspecies Hybrid Analysis Reveals Parent-Of-Origin Bias in the Mouse Placenta

To investigate the epigenetic landscape at the interface between mother and fetus, we provide a comprehensive analysis of parent of origin bias in the placenta. Using F1 interspecies hybrids, we sequenced RNA from 23 individual midgestation placentas, five late stage placentas, and two yolk sac samples and then used SNPs to determine whether transcripts were preferentially generated from the maternal or paternal allele. In the placenta, we find 103 genes that show significant and reproducible parent-of-origin bias, of which 78 are novel candidates. Most (96%) show a strong maternal bias which, using multiple models, we demonstrate is not due to maternal decidual contamination. Analysis of the X chromosome also reveals paternal expression of Xist and several genes that escape inactivation, most significantly Rps4x, Fhl1, and Slc38a5. Finally, sequencing individual placentas allowed us to reveal notable expression similarity between littermates. In all, we observe a striking preference for maternal transcription in the midgestation mouse placenta and a dynamic imprinting landscape in extraembryonic tissues, reflecting the complex nature of epigenetic pathways in the placenta. 3'-end Sequencing for Expression Quantification (3SEQ) and SNP Analysis to observe parent-of-origin bias in 28 placental samples at two time points and 2 yolk sac samples为探究母胎界面的表观遗传图谱（epigenetic landscape），我们针对胎盘中的亲本起源偏倚（parent-of-origin bias）开展了全面分析。本研究采用种间F1杂交模型，对23例妊娠中期胎盘、5例晚期妊娠胎盘以及2例卵黄囊样本的RNA进行测序，并通过单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs）判定转录本优先源自母本还是父本等位基因。 在胎盘中，我们共鉴定出103个存在显著且可重复的亲本起源偏倚的基因，其中78个为全新候选基因。其中绝大多数（96%）表现出强烈的母本表达偏倚，我们通过多种模型验证，该偏倚并非由母体蜕膜污染所致。 对X染色体的分析还显示，Xist以及多个逃避X染色体失活的基因存在父本表达，其中以Rps4x、Fhl1和Slc38a5最为显著。 最后，对单个胎盘的测序使我们得以揭示同窝幼崽胎盘间显著的表达相似性。 总体而言，我们在妊娠中期小鼠胎盘中观察到了显著的母本转录偏好，并在胚外组织中发现了动态变化的印记图谱，这反映了胎盘中表观遗传通路的复杂特性。 本研究通过用于表达定量的3'端测序（3SEQ）与单核苷酸多态性分析，对两个时间点的28例胎盘样本以及2例卵黄囊样本的亲本起源偏倚进行了观测。