Transcriptomic Characterization of the Human Cell Cycle in Individual Unsynchronized Cells. Issue 24 (8th December 2017)

• Record Type: Journal Article
• Authors: Karlsson, Joakim; Kroneis, Thomas; Jonasson, Emma; Larsson, Erik; Ståhlberg, Anders
• Is Part Of: Journal of molecular biology. Volume 429:Issue 24(2017)
• Page Start: 3909
• Page End: 3924
• Publication Date: 2017-12-08
• Subjects: hESC human embryonic stem cell -- GO Gene Ontology -- lncRNA long non-coding RNA -- miRNA microRNA -- MLS myxoid liposarcoma -- t-SNE t-distributed stochastic neighbor embedding; cell cycle -- unsynchronized -- gene expression dynamics -- transcription factors -- single-cell analysis; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2017.10.011
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The highly fine-tuned dynamics of cell cycle gene expression have been intensely studied for several decades. However, some previous observations may be difficult to fully decouple from artifacts induced by traditional cell synchronization procedures. In addition, bulk cell measurements may have disguised intricate details. Here, we address this by sorting and transcriptomic sequencing of single cells progressing through the cell cycle without prior synchronization. Genes and pathways with known cell cycle roles are confirmed, associated regulatory sequence motifs are determined, and we also establish ties between other biological processes and the unsynchronized cell cycle. Importantly, we find the G1 phase to be surprisingly heterogeneous, with transcriptionally distinct early and late time points. We additionally note that mRNAs accumulate to reach maximum total levels at mitosis and find that stable transcripts show reduced cell-to-cell variability, consistent with the transcriptional burst model of gene expression. Our study provides the first detailed transcriptional profiling of an unsynchronized human cell cycle. Graphical abstract: Highlights: An updated view of cell cycle gene expression, without synchronization artifacts Transcription factor and miRNA binding motifs associated with cell cycle expression Transcriptionally distinct early and late G1 subpopulations in single cells Total polyadenylated mRNA levels progressively increase toward mitosis. Support for the transcriptional burst model of gene expression