Quantitative analysis of circadian single cell oscillations in response to temperature

PLoS One. 2018 Jan 2;13(1):e0190004. doi: 10.1371/journal.pone.0190004. eCollection 2018.


Body temperature rhythms synchronize circadian oscillations in different tissues, depending on the degree of cellular coupling: the responsiveness to temperature is higher when single circadian oscillators are uncoupled. So far, the role of coupling in temperature responsiveness has only been studied in organotypic tissue slices of the central circadian pacemaker, because it has been assumed that peripheral target organs behave like uncoupled multicellular oscillators. Since recent studies indicate that some peripheral tissues may exhibit cellular coupling as well, we asked whether peripheral network dynamics also influence temperature responsiveness. Using a novel technique for long-term, high-resolution bioluminescence imaging of primary cultured cells, exposed to repeated temperature cycles, we were able to quantitatively measure period, phase, and amplitude of central (suprachiasmatic nuclei neuron dispersals) and peripheral (mouse ear fibroblasts) single cell oscillations in response to temperature. Employing temperature cycles of different lengths, and different cell densities, we found that some circadian characteristics appear cell-autonomous, e.g. period responses, while others seem to depend on the quality/degree of cellular communication, e.g. phase relationships, robustness of the oscillation, and amplitude. Overall, our findings indicate a strong dependence on the cell's ability for intercellular communication, which is not only true for neuronal pacemakers, but, importantly, also for cells in peripheral tissues. Hence, they stress the importance of comparative studies that evaluate the degree of coupling in a given tissue, before it may be used effectively as a target for meaningful circadian manipulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Circadian Rhythm*
  • Ear
  • Mice
  • Mice, Inbred C57BL
  • Temperature*

Grant support

The present study was supported by the Federal Ministry of Education and Research (BMBF) [grant number 01GQ1001C to H.H. and A.K.]. Work in A.K.'s laboratory is further supported by the German Science Foundation (DFG). U.A.'s salary was paid by the Federal Ministry of Education and Research [grant number 01GQ1001C] and by a research stipend granted by the Charité-Universitätsmedizin Berlin. J.K.S.'s salary was paid by the Federal Ministry of Education and Research [grant number 01GQ1001C]. The XR/Mega-10Z ICCD camera was funded by the German Science Foundation (DFG) [grant AB139/4-1 to U.A.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.