In recent years, allele-specific single-cell RNA-seq (scRNA-seq) analysis has demonstrated wide-spread dynamic random monoallelic expression of autosomal genes (aRME) in different cell types. However, the prevalence of dynamic aRME during pre-gastrulation development remains unknown. Here, we show that dynamic aRME is wide-spread in different lineages of pre-gastrulation embryos. Additionally, the origin of dynamic aRME remains poorly understood. Theoretically, it is believed that independent transcriptional bursting from each allele leads to the dynamic aRME. However, based on analysis of allele-specific burst kinetics of autosomal genes, we found that allelic burst is not perfectly independent, rather it happens in semi-coordinated fashion. Importantly, we show that semi-coordinated allelic bursting of the genes; particularly with low burst frequency, leads to frequent asynchronous allelic bursting, thereby shaping the landscape of dynamic aRME in pre-gastrulation embryos. Altogether, our study provides significant insight into the prevalence and origin of dynamic aRME and cell to cell expression heterogeneity during early mammalian development.

中文翻译：

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前胎胚中半协调等位基因突增形动态随机单等位基因表达

近年来，等位基因特异性单细胞RNA-seq（scRNA-seq）分析已证明常染色体基因（aRME）在不同细胞类型中的广泛动态随机单等位基因表达。然而，在孕前发育过程中动态aRME的患病率仍然未知。在这里，我们表明动态aRME广泛分布于胎前胚胎的不同谱系中。此外，动态aRME的起源仍然知之甚少。从理论上讲，据信来自每个等位基因的独立转录爆发导致动态的aRME。然而，基于对常染色体基因等位基因特异性爆发动力学的分析，我们发现等位基因爆发不是完全独立的，而是以半协调的方式发生的。重要的是，我们显示了基因的半协调等位基因爆发。特别是在低猝发频率下，会导致频繁的异步等位基因猝发，从而塑造了妊娠前胚胎中动态aRME的格局。总之，我们的研究为哺乳动物早期发育过程中动态aRME的流行和起源以及细胞间表达异质性提供了重要的见识。