The 4th dimension of in vitro systems – Time to level up

Mihelakis, Melina; Ndikung, Johanna; Oelgeschläger, Michael; Ertych, Norman

doi:10.1016/j.envint.2022.107256

Cited by 1 publication

(1 citation statement)

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“…The model qualitatively recapitulates critical observations and offers a blueprint for subsequent experiments to validate the induction and disruption of circadian rhythms in vitro or ex vivo by temperture rhythms. Our work contributes to the development of cell culture systems that can beter represent circadian biology (Mihelakis et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Mathematical modeling of temperature-induced circadian rhythms

Lu,

Li,

Schloss

et al. 2024

Front. Syst. Biol.

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The central circadian pacemaker in the suprachiasmatic nuclei (SCN) aligns the phase and period of autonomous molecular oscillators in peripheral cells to daily light/dark cycles via physiological, neuronal, hormonal, and metabolic signals. Among different entrainment factors, temperature entrainment has been proposed as an essential alternative for inducing and sustaining circadian rhythms in vitro. While the synchronization mechanisms for hormones such as glucocorticoids have been widely studied, little is known about the crucial role of body temperature as a systemic cue. In this work, we develop a semi-mechanistic mathematical model describing the entrainment of peripheral clocks to temperature rhythms. The model incorporates a temperature sensing-transduction cascade involving a heat shock transcription factor-1 (HSF1) and heat shock response (HSR) pathway to simulate the entrainment of clock genes. The model is used to investigate the mammalian temperature entrainment and synchronization of cells subject to temperature oscillations of different amplitudes and magnitudes and examine the effects of transitioning between temperature schedules. Our computational analyses of the system’s dynamic responses reveal that 1) individual cells gradually synchronize to the rhythmic temperature signal by resetting their intrinsic phases to achieve coherent dynamics while oscillations are abolished in the absence of temperature rhythmicity; 2) alterations in the amplitude and period of temperature rhythms impact the peripheral synchronization behavior; 3) personalized synchronization strategies allow for differential, adaptive responses to temperature rhythms. Our results demonstrate that temperature can be a potent entrainer of circadian rhythms. Therefore, in vitro systems subjected to temperature modulation can serve as a potential tool for studying the adjustment or disruption of circadian rhythms.

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Section: Discussionmentioning

confidence: 99%