Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells

PLoS One. 2017 Dec 11;12(12):e0188772. doi: 10.1371/journal.pone.0188772. eCollection 2017.

Abstract

The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchronized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development. Furthermore, the cell cycle synchronizes with the circadian clock, providing a possible link between developmental transcriptional networks and the cell cycle. In conclusion we find that cell cycle synchronized transcriptional patterns are temporally compartmentalized and more complex than previously anticipated, involving genes, which control cell identity and development.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Algorithms
  • Cell Cycle / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Transcription Factors / metabolism*
  • Transcriptome*

Substances

  • Cell Cycle Proteins
  • Transcription Factors

Grant support

The study was supported by grants from the Swedish Research Council (M.An), Swedish Cancer Foundation (P.S, M.An), Swedish Childhood Cancer Foundation (M.An), the Hållsten Research Foundation (M.Al), Swedish Society for Medical Research (C.M), The Swedish Brain Foundation (C.M), Knut & Alice Wallenberg Foundation (E.L), Grant Agency of the Czech Republic (GA15-20818S (M.An), GA15-21789S (V.B)), CEITEC 2020 (LQ1601) project with a financial contribution made by the Ministry of Education, Youths and Sports of the Czech Republic (KI-MU: CZ.1.07/2.3.00/20.0180 (V.B) with special financial support from the National Programme for Sustainability II, grant 15-11707S from the Czech Science Foundation (K.S), grants 15-28628A and 15-33999A from the Grant Agency for Health Research of the Czech Republic (K.S), by project LQ1605 from the National Program of Sustainability II (MEYS CR (K.S)), and by the project ICRC-ERA-Human Bridge (No. 316345) funded by the 7th Framework Programme of the European Union (K.S). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.