The effect of circadian rhythm on gene expression in human skin
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE112660 | GEO | 2018/11/13
REPOSITORIES: GEO
Similar Datasets
Project description:Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. Like other tissues, skin is subject to temporal fluctuations in physiological responses under both homeostatic and stressed states. To gain insight into these fluctuations, we investigated the role of the circadian clock in the transcriptional regulation of skin The purpose of this study was to gain insight into the evolutionarily-conserved rhythmic patterns of the circadian transcriptome in human skin and how it relates to published transcriptomes from other human tissues.
2020-07-20 | GSE139300 | GEO
Project description:Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. Like other tissues, skin is subject to temporal fluctuations in physiological responses under both homeostatic and stressed states. To gain insight into these fluctuations, we investigated the role of the circadian clock in the transcriptional regulation of skin The purpose of this study was to gain insight into the evolutionarily-conserved rhythmic patterns of the circadian transcriptome in human skin and how it relates to published transcriptomes from other human tissues.
2020-07-20 | GSE139301 | GEO
Project description:Various aspects of physiology and cell function present self-sustained ~24h variations termed circadian rhythms, enabling anticipation and adaptation to the 24-h cycle produced by the Earth’s rotation. The circadian clock system consists of a central clock located in the suprachiasmatic nucleus in the hypothalamus, and peripheral clocks present in distinct tissues. In particular, peripheral clocks in the liver have fundamental roles in maintaining liver homeostasis. Here, we established and characterized a human hepatocyte in vitro system in which human primary hepatocytes displayed self-sustained oscillations independently of external cues a distinguishing feature of circadian clocks. We then used this experimental system to study the impact of circadian oscillations in human liver pathophysiology. By generating hepatocyte circadian transcriptomes, we demonstrated that the transcriptional state of cultured human hepatocytes is dynamic across 24h. Analyses of gene expression data identified a set of cycling genes, including a subset of well-established ‘core clock genes’ and oscillating genes related to inflammation, drug metabolism, and energy homeostasis. We documented a circadian-dependent induction of the pro-inflammatory cytokines IL-1b, IL-6, TNF-a CXCLl1 and CXCL10 triggered by LPS or IFN-b in human hepatocytes. We also demonstrated circadian fluctuations of a subset of drug metabolism enzymes, which regulate drug pharmacokinetics. Among these enzymes, we identified CYP3A4, as one displaying circadian fluctuations at activity levels and a time-dependent induction with rifampin. Finally, we showed the impact of applying chronopharmacotherapy by designing a treatment protocol to minimize atorvastatin and acetaminophen induced hepatotoxicity. Collectively, our findings document that circadian time can influence the magnitude of the inflammatory response in the liver and the efficacy, toxicity, and/or the therapeutic index of drugs.
2024-02-28 | GSE218243 | GEO
Project description:Various aspects of physiology and cell function present self-sustained ~24h variations termed circadian rhythms, enabling anticipation and adaptation to the 24-h cycle produced by the Earth’s rotation. The circadian clock system consists of a central clock located in the suprachiasmatic nucleus in the hypothalamus, and peripheral clocks present in distinct tissues. In particular, peripheral clocks in the liver have fundamental roles in maintaining liver homeostasis. Here, we established and characterized a human hepatocyte in vitro system in which human primary hepatocytes displayed self-sustained oscillations independently of external cues a distinguishing feature of circadian clocks. We then used this experimental system to study the impact of circadian oscillations in human liver pathophysiology. By generating hepatocyte circadian transcriptomes, we demonstrated that the transcriptional state of cultured human hepatocytes is dynamic across 24h. Analyses of gene expression data identified a set of cycling genes, including a subset of well-established ‘core clock genes’ and oscillating genes related to inflammation, drug metabolism, and energy homeostasis. We documented a circadian-dependent induction of the pro-inflammatory cytokines IL-1b, IL-6, TNF-a CXCLl1 and CXCL10 triggered by LPS or IFN-b in human hepatocytes. We also demonstrated circadian fluctuations of a subset of drug metabolism enzymes, which regulate drug pharmacokinetics. Among these enzymes, we identified CYP3A4, as one displaying circadian fluctuations at activity levels and a time-dependent induction with rifampin. Finally, we showed the impact of applying chronopharmacotherapy by designing a treatment protocol to minimize atorvastatin and acetaminophen induced hepatotoxicity. Collectively, our findings document that circadian time can influence the magnitude of the inflammatory response in the liver and the efficacy, toxicity, and/or the therapeutic index of drugs.
2024-02-28 | GSE218242 | GEO
Project description:While several physiological skin parameters vary in a circadian manner, the identity of genes participating in chronobiology of skin remains unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle related genes, the former peaking during the day and the latter peaking at the night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes as keratinocyte-specific deletion of Bmal1 obliterates time of day dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. Consistent with higher cellular susceptibility to UV-induced DNA damage during S phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. As maximum numbers of keratinocytes go through S phase in the late afternoon in the human epidermis, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation such that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers. Whole skin was collected at 4 hour intervals for 48 hours. Where ZT number indicates the number of hours elapsed from when lights are switched on. ZT0 = lights on (6am). ZT12=lights off (6pm). Total RNA was purified from the skin of each mouse and equal amount of RNA from the 3 replicates for each time point were pooled. Telogen samples were collected from skin of P46 male mice.
2012-08-01 | E-GEOD-38622 | biostudies-arrayexpress
Project description:While several physiological skin parameters vary in a circadian manner, the identity of genes participating in chronobiology of skin remains unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle related genes, the former peaking during the day and the latter peaking at the night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes as keratinocyte-specific deletion of Bmal1 obliterates time of day dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. Consistent with higher cellular susceptibility to UV-induced DNA damage during S phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. As maximum numbers of keratinocytes go through S phase in the late afternoon in the human epidermis, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation such that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers. Whole skin was collected at 4 hour intervals for 48 hours. ZT number indicates the number of hours elapsed from when lights are switched on. ZT0 = lights on (6am). ZT12=lights off (6pm). Total RNA was purified from the skin of each mouse and equal amount of RNA from the 3 replicates for each time point were pooled. Anagen samples were collected from skin of P30 male mice.
2012-08-01 | E-GEOD-38623 | biostudies-arrayexpress
Project description:While several physiological skin parameters vary in a circadian manner, the identity of genes participating in chronobiology of skin remains unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle related genes, the former peaking during the day and the latter peaking at the night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes as keratinocyte-specific deletion of Bmal1 obliterates time of day dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. Consistent with higher cellular susceptibility to UV-induced DNA damage during S phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. As maximum numbers of keratinocytes go through S phase in the late afternoon in the human epidermis, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation such that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers. Whole skin was collected at ZT22. Where ZT number indicates the number of hours elapsed from when lights are switched on. ZT0 = lights on (6am). ZT12=lights off (6pm). Het mice designate a presence of one Bmal1 mutant allele and one wt allele. KO mice designate mice germline deleted for both copies of Bmal1 allele. Total RNA was purified from the skin of each biological littermate replicate.
2012-08-01 | E-GEOD-38624 | biostudies-arrayexpress
Project description:To delineate the in vivo function of NIPP1 in epidermal homeostasis, we generated skin-specific NIPP1 knockout (SKO) mice where NIPP1 is conditionally removed from keratinocytes. To gain unbiased insight into the molecular mechanism that underlies the hyperproliferation phenotype, we performed RNA-seq of the isolated epidermis of control (CTR) and SKO mice.
2020-05-14 | GSE116844 | GEO
Project description:The effect of circadian rhythm on gene expression in human skin.
| PRJNA579167 | ENA
Project description:The effect of circadian rhythm on gene expression in human skin
| PRJNA448675 | ENA