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Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle
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Feillet, C., Krusche, Peter, Tamanini, F., Janssens, R. C., Downey, Mike J., Martin, P., Teboul, M., Saito, S., Lévi, Francis A., Bretschneider, Till, van der Horst, G. T. J., Delaunay, F. and Rand, D. A. (David A.) (2014) Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle. Proceedings of the National Academy of Sciences of the United States of America, Volume 111 (Number 27). pp. 9828-9833. doi:10.1073/pnas.1320474111 ISSN 0027-8424.
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Official URL: http://dx.doi.org/10.1073/pnas.1320474111
Abstract
Daily synchronous rhythms of cell division at the tissue or organism level are observed in many species and suggest that the circadian clock and cell cycle oscillators are coupled. For mammals, despite known mechanistic interactions, the effect of such coupling on clock and cell cycle progression, and hence its biological relevance, is not understood. In particular, we do not know how the temporal organization of cell division at the single-cell level produces this daily rhythm at the tissue level. Here we use multispectral imaging of single live cells, computational methods, and mathematical modeling to address this question in proliferating mouse fibroblasts. We show that in unsynchronized cells the cell cycle and circadian clock robustly phase lock each other in a 1:1 fashion so that in an expanding cell population the two oscillators oscillate in a synchronized way with a common frequency. Dexamethasone-induced synchronization reveals additional clock states. As well as the low-period phase-locked state there are distinct coexisting states with a significantly higher period clock. Cells transition to these states after dexamethasone synchronization. The temporal coordination of cell division by phase locking to the clock at a single-cell level has significant implications because disordered circadian function is increasingly being linked to the pathogenesis of many diseases, including cancer.
Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle.. Available from: https://www.researchgate.net/publication/264641131_Phase_locking_and_multiple_oscillating_attractors_for_the_coupled_mammalian_clock_and_cell_cycle [accessed Apr 8, 2015].
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre | ||||||||
| Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America | ||||||||
| Publisher: | National Academy of Sciences | ||||||||
| ISSN: | 0027-8424 | ||||||||
| Official Date: | 8 July 2014 | ||||||||
| Dates: |
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| Volume: | Volume 111 | ||||||||
| Number: | Number 27 | ||||||||
| Page Range: | pp. 9828-9833 | ||||||||
| DOI: | 10.1073/pnas.1320474111 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access |
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