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Transcriptomic Characterization of the Human Cell Cycle in Individual Unsynchronized Cells.

Journal article
Authors Joakim Karlsson
Thomas Kroneis
Emma Jonasson
Erik Larsson
Anders Ståhlberg
Published in Journal of molecular biology
Volume 429
Issue 24
Pages 3909-3924
ISSN 1089-8638
Publication year 2017
Published at Institute of Biomedicine, Department of Pathology
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 3909-3924
Language en
Links dx.doi.org/10.1016/j.jmb.2017.10.01...
www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Biomarkers, Tumor, genetics, Cell Cycle, genetics, Gene Expression Profiling, Humans, Liposarcoma, Myxoid, genetics, pathology, Mitosis, genetics, Single-Cell Analysis, methods, Transcriptome, Tumor Cells, Cultured
Subject categories Cell and Molecular Biology

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.

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