Nick Melosh describes a method for sampling RNA and proteins from cells using nanostraws.
New Research In
Physical Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved January 23, 2013 (received for review October 3, 2012)
Significance
Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, but the mechanisms involved remain largely unexplored. We show that one wk of insufficient sleep alters gene expression in human blood cells, reduces the amplitude of circadian rhythms in gene expression, and intensifies the effects of subsequent acute total sleep loss on gene expression. The affected genes are involved in chromatin remodeling, regulation of gene expression, and immune and stress responses. The data imply molecular mechanisms mediating the effects of sleep loss on health and highlight the interrelationships between sleep homeostasis, circadian rhythmicity, and metabolism.
Abstract
Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.
Footnotes
↵1C.S.M.-L., S.N.A., G.B., C.P.S., and D.-J.D. contributed equally to this work.
- ↵2To whom correspondence should be addressed. E-mail: d.j.dijk{at}surrey.ac.uk.
Author contributions: S.N.A., E.E.L., M.v.S., C.P.S., and D.-J.D. designed research; C.S.M.-L., G.B., E.E.L., A.S., R.K., J.C.Y.L., and N.S. performed research; C.S.M.-L., G.B., E.E.L., A.S., and R.K. analyzed data; and C.S.M.-L., S.N.A., E.E.L., M.v.S., C.P.S., and D.-J.D. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE39445). Custom microarray design deposited at GEO (accession no. GPL15331).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1217154110/-/DCSupplemental.
Freely available online through the PNAS open access option.
Sleep loss and the human blood transcriptome
More Articles of This Classification
Related Content
Cited by...
- Universal method for robust detection of circadian state from gene expression
- Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome
- Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome
- Diurnal transcriptome atlas of a primate across major neural and peripheral tissues
- Hormonally mediated effects of artificial light at night on behavior and fitness: linking endocrine mechanisms with function
- CYCLOPS reveals human transcriptional rhythms in health and disease
- MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression
- Endocrine and metabolic diurnal rhythms in young adult men born small vs appropriate for gestational age
- Circadian Rhythms, Metabolism, and Chrononutrition in Rodents and Humans
- Light at night, clocks and health: from humans to wild organisms
- Disrupted Sleep: From Molecules to Cognition
- Electric light, particularly at night, disrupts human circadian rhythmicity: is that a problem?
- Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt
- Alterations in diurnal rhythmicity in patients treated for nonfunctioning pituitary macroadenoma: a controlled study and literature review
- Effect of sleep deprivation on the human metabolome
- Timing Is Everything: Implications for Metabolic Consequences of Sleep Restriction
- PNAS Plus: From the Cover: Mistimed sleep disrupts circadian regulation of the human transcriptome
Similar Articles
You May Also be Interested in
PNAS Profile with NAS member and mathematician Yuval Peres
Researchers report evidence in yeast cells that nucleosomes inhibit binding and cleavage by the genome-editing enzyme CRISPR-Cas9, suggesting nucleosome position maps might help improve genome-editing efficiency.
Image courtesy of Janet Iwasa (University of Utah, Salt Lake City).
A study exploring intergenerational social mobility in the United States finds that fewer people born in the 1980s were upwardly mobile than those born in the 1940s and that the slowing of status mobility accentuates inequalities of opportunity.
Image courtesy of Pixabay/Ponciano.
A study suggests that social learning from exposure to opposing political views on social networks can improve accuracy and remove partisan bias, but displaying political symbols during cross-party communication can prevent such learning, according to the authors.
