Robust synchronization of coupled circadian and cell cycle oscillators in single mammalian cells. Issue 7 (15th July 2014)

• Record Type: Journal Article
• Authors: Bieler, Jonathan; Cannavo, Rosamaria; Gustafson, Kyle; Gobet, Cedric; Gatfield, David; Naef, Felix
• Is Part Of: Molecular systems biology. Volume 10:Issue 7(2014)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2014-07-15
• Subjects: Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.20145218
• Languages: English
• ISSNs: 1744-4292

Abstract

<abstract abstract-type="main" id="msb145218-abs-0001"> <title>Abstract</title> <p>Circadian cycles and cell cycles are two fundamental periodic processes with a period in the range of 1 day. Consequently, coupling between such cycles can lead to synchronization. Here, we estimated the mutual interactions between the two oscillators by time‐lapse imaging of single mammalian NIH3T3 fibroblasts during several days. The analysis of thousands of circadian cycles in dividing cells clearly indicated that both oscillators tick in a 1:1 mode‐locked state, with cell divisions occurring tightly 5 h before the peak in circadian <italic>Rev‐Erb</italic>α‐YFP reporter expression. In principle, such synchrony may be caused by either unidirectional or bidirectional coupling. While gating of cell division by the circadian cycle has been most studied, our data combined with stochastic modeling unambiguously show that the reverse coupling is predominant in NIH3T3 cells. Moreover, temperature, genetic, and pharmacological perturbations showed that the two interacting cellular oscillators adopt a synchronized state that is highly robust over a wide range of parameters. These findings have implications for circadian function in proliferative tissues, including epidermis, immune cells, and cancer.</p> </abstract>