Dissecting the autonomy of the liver circadian clock
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA481257 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7524830_1.fastq.gz | Fastqsanger.gz | |||
| SRR7524830_2.fastq.gz | Fastqsanger.gz | |||
| SRR7524840_1.fastq.gz | Fastqsanger.gz | |||
| SRR7524840_2.fastq.gz | Fastqsanger.gz | |||
| SRR7524850_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 108 |
Similar Datasets
Project description:The mammalian circadian clock system is made up of individual cell and tissue clocks that function as a coherent network, however it remains unclear which rhythmic functions of the liver clock are autonomous or rely on clocks in other tissues. Here, using mice which only have a functioning liver clock, we investigate the autonomous vs non-autonomous reatures of the liver clock and diurnal rhythmicity in the liver
2019-06-11 | GSE117134 | GEO
Project description:Mammals rely on a network of circadian clocks to control daily systemic metabolism and physiology. The central pacemaker in the suprachiasmatic nucleus (SCN) is considered hierarchically dominant over peripheral clocks, whose degree of independence, or tissue-level autonomy, has never been ascertained in vivo. Using arrhythmic Bmal1-null mice, we generated animals with reconstituted circadian expression of BMAL1 exclusively in the liver (Liver-RE). High-throughput transcriptomics and metabolomics show that the liver has independent circadian functions specific for metabolic processes such as the NAD+ salvage pathway and glycogen turnover. However, although BMAL1 occupies chromatin at most genomic targets in Liver-RE mice, circadian expression is restricted to ∼10% of normally rhythmic transcripts. Finally, rhythmic clock gene expression is lost in Liver-RE mice under constant darkness. Hence, full circadian function in the liver depends on signals emanating from other clocks, and light contributes to tissue-autonomous clock function.
2019-06-13 | GSE132659 | GEO
Project description:As a circadian organ, liver executes diverse functions in different phase of the circadian clock. This process is believed to be driven by a transcription program. Here, we present a TF DNA-binding activity centered multi-dimensional proteomics landscape, including DNA-binding activity of TFs, the phosphorylation pattern, ubiquitylation pattern, the nuclear sub-proteome, the whole proteome as well as the transcriptome, to portrait the hierarchical circadian clock network of mouse liver. The TF DNA-binding activity indicates diurnal oscillation in four major pathways, immune response, glucose metabolism, fatty acid metabolism, and the cell cycle. We also isolated the mouse liver Kupffer cells and measured their proteomes in the circadian clock to reveal cell type resolved circadian clock. These are the most comprehensive datasets for circadian clock in the mouse liver and provided the richest data resource for the understanding of mouse liver physiology around the circadian clock.
2018-06-25 | PXD008771 |
Project description:As a circadian organ, liver executes diverse functions in different phase of the circadian clock. This process is believed to be driven by a transcription program. Here, we present a TF DNA-binding activity centered multi-dimensional proteomics landscape, including DNA-binding activity of TFs, the phosphorylation pattern, ubiquitylation pattern, the nuclear sub-proteome, the whole proteome as well as the transcriptome, to portrait the hierarchical circadian clock network of mouse liver. The TF DNA-binding activity indicates diurnal oscillation in four major pathways, immune response, glucose metabolism, fatty acid metabolism, and the cell cycle. We also isolated the mouse liver Kupffer cells and measured their proteomes in the circadian clock to reveal cell type resolved circadian clock. These are the most comprehensive datasets for circadian clock in the mouse liver and provided the richest data resource for the understanding of mouse liver physiology around the circadian clock.
2018-06-25 | PXD008862 |
Project description:Circadian rhythms are integral to maintaining metabolic health by temporally coordinating metabolic functions across tissues. However, the mechanisms underlying circadian cross-tissue coordination remain poorly understood. In this study, we uncover a central role for the liver clock in regulating circadian rhythms in white adipose tissue (WAT). Using a liver-specific Bmal1 knockout mouse model, we show that hepatic circadian control is crucial for lipid metabolism in WAT. In addition, by utilizing a model where functional clocks are restricted to the liver, we demonstrate that the liver clock alone drives circadian gene expression in WAT, including Cebpa, a key regulator of adipogenesis. Mechanistically, we show that circadian liver-to-WAT communication is mediated through secreted proteins, including the adaptor protein 14-3-3η (Ywhah). The clinical relevance of these findings is supported by human cohort data, which correlate liver YWHAH expression with lipid metabolic pathways in WAT and cardiometabolic risk factors. These findings provide a mechanistic framework for how the liver clock coordinates WAT physiology and highlights its central role in cardiometabolic health, offering potential insights for targeted circadian-based therapies for metabolic disorders.
2025-02-11 | GSE288748 | GEO
Project description:Circadian rhythms are integral to maintaining metabolic health by temporally coordinating metabolic functions across tissues. However, the mechanisms underlying circadian cross-tissue coordination remain poorly understood. In this study, we uncover a central role for the liver clock in regulating circadian rhythms in white adipose tissue (WAT). Using a liver-specific Bmal1 knockout mouse model, we show that hepatic circadian control is crucial for lipid metabolism in WAT. In addition, by utilizing a model where functional clocks are restricted to the liver, we demonstrate that the liver clock alone drives circadian gene expression in WAT, including Cebpa, a key regulator of adipogenesis. Mechanistically, we show that circadian liver-to-WAT communication is mediated through secreted proteins, including the adaptor protein 14-3-3η (Ywhah). The clinical relevance of these findings is supported by human cohort data, which correlate liver YWHAH expression with lipid metabolic pathways in WAT and cardiometabolic risk factors. These findings provide a mechanistic framework for how the liver clock coordinates WAT physiology and highlights its central role in cardiometabolic health, offering potential insights for targeted circadian-based therapies for metabolic disorders.
2025-02-11 | GSE288746 | GEO
Project description:Circadian rhythms are integral to maintaining metabolic health by temporally coordinating metabolic functions across tissues. However, the mechanisms underlying circadian cross-tissue coordination remain poorly understood. In this study, we uncover a central role for the liver clock in regulating circadian rhythms in white adipose tissue (WAT). Using a liver-specific Bmal1 knockout mouse model, we show that hepatic circadian control is crucial for lipid metabolism in WAT. In addition, by utilizing a model where functional clocks are restricted to the liver, we demonstrate that the liver clock alone drives circadian gene expression in WAT, including Cebpa, a key regulator of adipogenesis. Mechanistically, we show that circadian liver-to-WAT communication is mediated through secreted proteins, including the adaptor protein 14-3-3η (Ywhah). The clinical relevance of these findings is supported by human cohort data, which correlate liver YWHAH expression with lipid metabolic pathways in WAT and cardiometabolic risk factors. These findings provide a mechanistic framework for how the liver clock coordinates WAT physiology and highlights its central role in cardiometabolic health, offering potential insights for targeted circadian-based therapies for metabolic disorders.
2025-02-11 | GSE288747 | GEO
Project description:The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high fat diet, the gut microbiota drives PPARγ-mediated activation of newly oscillatory transcriptional programs in the liver. Moreover, antibiotics treatment prevents PPARγ-driven transcription in the liver, underscoring the essential role of gut microbes in clock reprogramming and hepatic circadian homeostasis. Thus, a specific molecular signature characterizes the influence of the gut microbiome in the liver, leading to the transcriptional rewiring of hepatic metabolism. We used microarray to quantify the tissue specific expression level of circadian genes in terms of total RNA.
2016-06-04 | GSE82250 | GEO
Project description:Circadian clocks drive 24-h rhythms of physiology and behavior. The circadian clock of hepatocytes has been shown to regulate glucose metabolism, and we were interested if rescuing liver clock function can reverse metabolic impairments in hyperphagic/obese Clock-D19 mutant mice. We compared transcripomte regulation in livers (at Zeitgeber time ZT10) of wild-type (C57BL/6J) and Clock-D19 mice and Clock-D19 mice with genetic rescue of liver clock function using hydrodynamic tail vein injection of a WT-CLOCK expression plasmid
2017-03-31 | GSE94838 | GEO
Project description:The circadian system plays an essential role in regulating timing of body metabolism in humans. Indeed, circadian misalignments are strongly associated with high rates of metabolic disorders. Molecular makeup of the circadian oscillator can be deciphered in cells cultured in vitro, and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo.
We aimed at assessing molecular clock properties in dermal fibroblasts established from the skin biopsies of seventeen Type 2 diabetic obese and non-obese patients and eleven healthy controls. Following in vitro synchronization, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters.
We observed a strong inverse correlation between HbA1c values and circadian period length within cells from the Type 2 diabetic group. RNA sequencing analysis conducted in this group samples revealed that ICAM1 encoding for the endothelial adhesion protein was differentially expressed between Type 2 diabetic compensated and non-compensated fibroblasts, and correlated with the period length. Furthermore, ICAM1 expression is driven by rhythmic CLOCK binding.
We provide for the first time a potential molecular link between severity of Type 2 diabetes and circadian clock machinery, which paves a way for further mechanistic understanding of circadian oscillator changes upon Type 2 diabetes in humans.
| EGAS00001003622 | EGA