Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle

Autor: Shoko Saito, Mike J. Downey, Céline Feillet, Patrick Martin, Filippo Tamanini, Michèle Teboul, Francis Lévi, Gijsbertus T. J. van der Horst, Franck Delaunay, Roel C. Janssens, Peter Krusche, Till Bretschneider, David A. Rand
Přispěvatelé: Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Molecular Genetics
Rok vydání: 2014
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America
Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2014, 111 (27), pp.9828-33
Proceedings of the National Academy of Sciences of the U.S.A., 111(27), 9828-9833. National Academy of Sciences
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.1320474111
Popis: International audience; 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.
Databáze: OpenAIRE