Naik Hemant Chandru, Hari Kishore, Chandel Deepshikha, Mandal Susmita, Jolly Mohit Kumar, Gayen Srimonta
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
iScience. 2021 Aug 5;24(9):102954. doi: 10.1016/j.isci.2021.102954. eCollection 2021 Sep 24.
Recently, allele-specific single-cell RNA-seq analysis has demonstrated widespread dynamic random monoallelic expression of autosomal genes (aRME) in different cell types. However, the prevalence of dynamic aRME during pregastrulation remains unknown. Here, we show that dynamic aRME is widespread in different lineages of pregastrulation embryos. Additionally, the origin of dynamic aRME remains elusive. It is believed that independent transcriptional bursting from each allele leads to dynamic aRME. Here, we show that allelic burst is not perfectly independent; instead it happens in a semicoordinated fashion. Importantly, we show that semicoordinated allelic bursting of genes, particularly with low burst frequency, leads to frequent asynchronous allelic bursting, thereby contributing to dynamic aRME. Furthermore, we found that coordination of allelic bursting is lineage specific and genes regulating the development have a higher degree of coordination. Altogether, our study provides significant insights into the prevalence and origin of dynamic aRME and their developmental relevance during early development.
最近，等位基因特异性单细胞RNA测序分析表明，常染色体基因（aRME）在不同细胞类型中存在广泛的动态随机单等位基因表达。然而，原肠胚形成前动态aRME的普遍性仍然未知。在这里，我们表明动态aRME在原肠胚形成前胚胎的不同谱系中广泛存在。此外，动态aRME的起源仍然难以捉摸。人们认为每个等位基因的独立转录爆发导致了动态aRME。在这里，我们表明等位基因爆发并非完全独立；相反，它以半协调的方式发生。重要的是，我们表明基因的半协调等位基因爆发，特别是爆发频率较低的情况，会导致频繁的异步等位基因爆发，从而促成动态aRME。此外，我们发现等位基因爆发的协调性是谱系特异性的，并且调控发育的基因具有更高程度的协调性。总之，我们的研究为动态aRME在早期发育过程中的普遍性和起源及其发育相关性提供了重要见解。
