文章基本信息

标题：The Contribution of lincRNAs at the Interface between Cell Cycle Regulation and Cell State Maintenance
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作者：Adriano Biasini ; Adam Alexander Thil Smith ; Baroj Abdulkarim 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：7
页码：1-29
DOI：10.1016/j.isci.2020.101291
语种：English
出版社：Elsevier
摘要：SummaryCell 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.Graphical AbstractDisplay OmittedHighlights•Genes differentially expressed between mESC cell cycle stages are enriched in lincRNAs•CC-lincRNAs are co-expressed with cell cycle and pluripotency genes•CC-lincRNAs are often mESC specific and their promoters enriched in pluripotency TFs•Upregulation of two CC-lincRNAs results in deregulated mESC cell cycle progressionMolecular Biology; Cell Biology