Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome

May 9, 2018Proceedings of the National Academy of Sciences of the United States of America

Night shift work disrupts daily gene activity rhythms in human immune cells

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Abstract

Four days of simulated night shifts resulted in a marked reduction of rhythmic transcripts in the human transcriptome.

A total of 73% of transcripts that were rhythmically expressed before night shifts continued to show rhythmicity during the night shift condition.
The remaining rhythmic transcripts exhibited lower amplitudes, indicating dampened rhythms rather than a complete loss of rhythmicity.
Key biological processes affected by the night shift protocol include the immune response mediated by natural killer cells and specific cellular signaling pathways.
These findings suggest that misalignment of circadian rhythms may disrupt physiological functions and could contribute to health issues associated with night shift work.

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Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.

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Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome

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