Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hepatocyte SREBP signaling mediates clock communication within the liver [RNA-seq]

ABSTRACT: Rhythmic intraorgan communication coordinates environmental signals and cell-intrinsic clock to maintain organ homeostasis. Hepatocyte-specific knockout of core components of the molecular clock, Rev-erba and b (ReverbhDKO), alters cholesterol and lipid metabolism in hepatocytes as well as rhythmic gene expression in non-parenchymal cells (NPC) of the liver. Here we report that in diet induced obesity (DIO)-caused fatty liver, hepatocyte SREBP cleavage-activating protein (SCAP) is required for ReverbhDKO-induced diurnal rhythmic remodeling and epigenomic reprogramming in Kupffer cells (KC). Integrative analyses of isolated hepatocytes and Kupffer cells uncovered potential signals, including secreted polypeptides and metabolites, that gain rhythmicity in the absence of REV-ERBs in a SCAP-dependent manner. These results shed light on the signaling mechanisms by which hepatocytes regulate diurnal rhythms in NPCs in DIO and fatty liver disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE206316 | GEO | 2023/04/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hepatocyte SREBP signaling mediates clock communication within the liver [ATAC-seq]

Project description:Rhythmic intraorgan communication coordinates environmental signals and cell-intrinsic clock to maintain organ homeostasis. Hepatocyte-specific knockout of core components of the molecular clock, Rev-erba and b (ReverbhDKO), alters cholesterol and lipid metabolism in hepatocytes as well as rhythmic gene expression in non-parenchymal cells (NPC) of the liver. Here we report that in diet induced obesity (DIO)-caused fatty liver, hepatocyte SREBP cleavage-activating protein (SCAP) is required for ReverbhDKO-induced diurnal rhythmic remodeling and epigenomic reprogramming in Kupffer cells (KC). Integrative analyses of isolated hepatocytes and Kupffer cells uncovered potential signals, including secreted polypeptides and metabolites, that gain rhythmicity in the absence of REV-ERBs in a SCAP-dependent manner. These results shed light on the signaling mechanisms by which hepatocytes regulate diurnal rhythms in NPCs in DIO and fatty liver disease.

2023-04-04 | GSE206318 | GEO

Hepatocyte SREBP signaling mediates clock communication within the liver [scRNA-seq]

2023-04-04 | GSE206317 | GEO

The Hepatocyte Clock and Feeding Interdependently Control Chrono-Homeostasis of Multiple Liver Cell Types (single nuclei RNA-seq)

Project description:Most cells in the body contain a cell autonomous molecular clock, but the requirement of peripheral clocks for circadian rhythmicity, and their effects on physiology, are not well understood. Here we show that deletion of core clock components REV-ERBa and b in adult mouse hepatocytes caused the loss of circadian rhythmicity of many liver genes, as expected, but also led to maintained and even gained rhythmicity of other genes without altering feeding behavior. The loss of REV-ERBs from hepatocytes leads to an exaggerated circadian rhythm of de novo lipogenesis and serum triglyceride levels. It is increasingly recognized that liver function is also influenced by non-hepatocytic cells, and remarkably the loss of REV-ERBs in hepatocytes remodeled the circadian transcriptomes of multiple cell types within the liver without altering their core clocks, indicating that hepatocytes communicated time signals to the non-hepatocytic cells. Finally, alteration of food availability, which is the dominant zeitgeber in the liver, demonstrated strong interdependence of the cell-autonomous hepatocyte clock mechanism and non-cell-autonomous environmental change. Together these studies reveal the interdependence of endogenous hepatocyte clocks and feeding entrainment on the regulation of circadian rhythms of multiple cell types in the liver.

2020-07-30 | GSE143526 | GEO

The Hepatocyte Clock and Feeding Interdependently Control Chrono-Homeostasis of Multiple Liver Cell Types (ATAC-seq)

2020-07-30 | GSE143525 | GEO

The Hepatocyte Clock and Feeding Interdependently Control Chrono-Homeostasis of Multiple Liver Cell Types (RNA-seq)

2020-07-30 | GSE143524 | GEO

Transcription profiling of mouse liver cells with a conditionally active liver clock to descriminate between rhythmic gene expression driven by cyclic systemic cues and local oscillators

Project description:The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) that synchronizes self-sustained oscillators in most peripheral cells. Rhythmic gene expression in peripheral tissues can be driven by cyclic systemic cues emanating from the SCN or by local oscillators. To discriminate between these two mechanisms, we engineered a mouse strain with a conditionally active liver clock. Transcriptome profiling revealed that the circadian transcription of most genes depends on functional hepatocyte clocks. However, the expression of 31 genes, including mPer2, oscillates robustly in clock-arrested hepatocytes. Such genes may be implicated in the synchronization of liver oscillators

2006-12-30 | E-MEXP-842 | biostudies-arrayexpress

Dissecting the autonomy of the liver circadian clock

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

An Intrinsically Disordered Region Controlling Condensation of a Circadian Clock Component and Rhythmic Transcription in the Liver [ChIP-seq]

Project description:Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBalpha, a repressive component of the molecular clock, forms circadian condensates in the nuclei of mouse Liver. These condensates are dictated by an intrinsically disordered region (IDR) located in the protein’s hinge region which specifically concentrates nuclear receptor corepressor 1 (NCOR1) at the genome. IDR deletion diminishes the recruitment of NCOR1 and disrupts rhythmic gene transcription in vivo. REV-ERBalpha condensates are located at high-order transcriptional repressive hubs in the Liver genome that are highly correlated with circadian gene repression. Deletion of the IDR disrupts transcriptional repressive hubs and diminishes silencing of target genes by REV-ERBalpha. This work demonstrates physiological circadian protein condensates containing REV-ERBalpha whose IDR is required for hub formation and the control of rhythmic gene expression.

2024-11-05 | GSE242901 | GEO

An Intrinsic Disorder Region Controlling Condensation of a Circadian Clock Component and Rhythmic Transcription in the Liver [RNA-seq]

Project description:Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBa, a repressive component of the molecular clock, forms circadian condensates in the nuclei of mouse liver. These condensates are dictated by an intrinsically disordered region (IDR) located in the protein’s hinge region which specifically concentrates nuclear receptor corepressor 1 (NCOR1) at the genome. IDR deletion diminishes the recruitment of NCOR1 and disrupts rhythmic gene transcription in vivo. REV-ERBa condensates are located at high-order transcriptional repressive hubs in the liver genome that are highly correlated with circadian gene repression. Deletion of the IDR disrupts transcriptional repressive hubs and diminishes silencing of target genes by REV-ERBa. This work demonstrates physiological circadian protein condensates containing REV-ERBa whose IDR is required for hub formation and the control of rhythmic gene expression.

2024-11-05 | GSE202605 | GEO

An Intrinsic Disorder Region Controlling Condensation of a Circadian Clock Component and Rhythmic Transcription in the Liver [ChIA-PET]

Project description:Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBalpha, a repressive component of the molecular clock, forms circadian condensates in the nuclei of mouse liver. These condensates are dictated by an intrinsically disordered region (IDR) located in the protein’s hinge region which specifically concentrates nuclear receptor corepressor 1 (NCOR1) at the genome. IDR deletion diminishes the recruitment of NCOR1 and disrupts rhythmic gene transcription in vivo. REV-ERBalpha condensates are located at high-order transcriptional repressive hubs in the liver genome that are highly correlated with circadian gene repression. Deletion of the IDR disrupts transcriptional repressive hubs and diminishes silencing of target genes by REV-ERBalpha. This work demonstrates physiological circadian protein condensates containing REV-ERBalpha whose IDR is required for hub formation and the control of rhythmic gene expression.

2024-11-05 | GSE242895 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data