Constraint and divergence of global gene expression in the mammalian embryo

We profiled genome-wide gene expression of 170 individual mid-gestation (embryonic day 11.5) whole mouse embryos derived from a 2-generation interspecies mouse cross and asked to what extent genetic variation drives four important parameters of regulatory architecture: allele-specific expression (ASE), imprinting, trans-regulatory effects, and maternal effect. The inbred strain C57BL/6J and wild-derived inbred strain CAST/EiJ were used in reciprocal crosses to generate F1 embryos. F1 progeny were backcrossed to C57BL/6J in reciprocal crosses to generate 154 N2 embryos. We employed a backcross design, in which N2 offspring have genotypically distinct parents, to enable comparison of gene expression for offspring from each side of the reciprocal cross. Our findings demonstrate that genetic variation contributes to widespread gene expression differences during mammalian embryogenesis. Transcriptome analysis of E11.5 mouse embryos: 16 F1 embryos from reciprocally crossed C57BL/6J and CastEi/J parents; and 154 N2 embryos from reciprocal backcross of F1s to the C57BL/6J parent.我们对170个个体妊娠中期（胚胎日11.5）的完整小鼠胚胎开展了全基因组基因表达谱分析，这些胚胎源自两代种间小鼠杂交。本研究旨在明确遗传变异对调控架构四项关键参数的影响程度，分别为：等位基因特异性表达（allele-specific expression, ASE）、基因组印记（imprinting）、反式调控效应（trans-regulatory effects）以及母源效应（maternal effect）。 本研究使用近交品系C57BL/6J与野生来源近交品系CAST/EiJ进行正反交，以制备子一代（F1）胚胎；随后将F1后代与C57BL/6J进行正反交回交，最终获得154个回交二代（N2）胚胎。本研究采用的回交设计中，N2后代的亲本基因型存在显著差异，可用于对比正反交双方后代的基因表达水平。 本研究结果证实，遗传变异在哺乳动物胚胎发生过程中可引发广泛的基因表达差异。本数据集包含E11.5小鼠胚胎的转录组分析数据：分别为来自正反交C57BL/6J与CAST/EiJ亲本的16个F1胚胎，以及将F1与C57BL/6J亲本进行正反交回交得到的154个N2胚胎。