Biasini Adriano, Smith Adam Alexander Thil, Abdulkarim Baroj, Ferreira da Silva Maria, Tan Jennifer Yihong, Marques Ana Claudia
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
iScience. 2020 Jul 24;23(7):101291. doi: 10.1016/j.isci.2020.101291. Epub 2020 Jun 20.
Cell cycle progression is controlled by the interplay of established cell cycle regulators. Changes in these regulators' activity underpin differences in cell cycle kinetics between cell types. We investigated whether long intergenic noncoding RNAs (lincRNAs) contribute to embryonic stem cell cycle adaptations. Using single-cell RNA sequencing data for mouse embryonic stem cells (mESCs) staged as G1, S, or G2/M we found differentially expressed lincRNAs are enriched among cell cycle-regulated genes. These lincRNAs (CC-lincRNAs) are co-expressed with genes involved in cell cycle regulation. We tested the impact of two CC-lincRNA candidates and show using CRISPR activation that increasing their expression is associated with deregulated cell cycle progression. Interestingly, CC-lincRNAs are often differentially expressed between G1 and S, their promoters are enriched in pluripotency transcription factor (TF) binding sites, and their transcripts are frequently co-regulated with genes involved in the maintenance of pluripotency, suggesting a contribution of CC-lincRNAs to mESC cell cycle adaptations.
细胞周期进程受既定细胞周期调节因子相互作用的控制。这些调节因子活性的变化是不同细胞类型之间细胞周期动力学差异的基础。我们研究了长链基因间非编码RNA（lincRNA）是否有助于胚胎干细胞周期适应。利用处于G1、S或G2/M期的小鼠胚胎干细胞（mESC）的单细胞RNA测序数据，我们发现差异表达的lincRNA在细胞周期调控基因中富集。这些lincRNA（CC-lincRNA）与参与细胞周期调控的基因共表达。我们测试了两个CC-lincRNA候选物的影响，并使用CRISPR激活表明增加它们的表达与细胞周期进程失调有关。有趣的是，CC-lincRNA在G1期和S期之间通常差异表达，它们的启动子富含多能性转录因子（TF）结合位点，并且它们的转录本经常与参与维持多能性的基因共同调控，这表明CC-lincRNA对mESC细胞周期适应有贡献。
