PRDM16 represses the type I Interferon response in adipocytes to promote mitochondrial and thermogenic programing
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ABSTRACT:
PROVIDER: PRJNA339992 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4054620.fastq.gz | Fastqsanger.gz | |||
| SRR4054621.fastq.gz | Fastqsanger.gz | |||
| SRR4054622.fastq.gz | Fastqsanger.gz | |||
| SRR4054623.fastq.gz | Fastqsanger.gz |
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Project description:PRDM16 is a strong activator of brown fat-specific genes, while also a repressor of white fat and muscle-specific genes. We asked what other pathways are regulated by PRDM16 in adipocytes that may be critical for brown and/or beige adipogenesis. Using microarray, we found PRDM16 also represses type I Interferon-stimulated genes (ISGs) in adipocytes.
2017-04-10 | GSE86016 | GEO
Project description:Brown adipose has the potential to counteract obesity, and thus, identifying signaling pathways that regulate the activity of this tissue is of great clinical interest. PRDM16 is a transcription factor that activates brown fat-specific genes while repressing white fat and muscle-specific genes in adipocytes. Whether PRDM16 also controls other gene programs to regulate adipocyte function was unclear. Here, we identify a novel role for PRDM16 in suppressing type I interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro and in vivo Ectopic activation of type I IFN signaling in brown adipocytes induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1) expression. Prdm16-deficient adipose displays an exaggerated response to type I IFN, including higher STAT1 levels and reduced mitochondrial gene expression. Mechanistically, PRDM16 represses ISGs through binding to promoter regions of these genes and blocking the activating function of IFN regulatory factor 1 (IRF1). Together, these data indicate that PRDM16 diminishes responsiveness to type I IFN in adipose cells to promote thermogenic and mitochondrial function.
| S-EPMC5452012 | biostudies-literature
Project description:Gene expression profile from brown adipose tissues of Prdm16 knockout and wile type mice. Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development. Brown adipose tissues were collected from Prdm16 knockout and wiletype mice with 4 biological replicates per condition. Experiment was done in two separate batch for 6-week-old and 11-month-old. Extracted RNA was hybridized to Agilent two-color arrays.
2014-04-09 | E-GEOD-55080 | biostudies-arrayexpress
Project description:Gene expression profile from brown adipose tissues of Prdm16 knockout and wile type mice. Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development.
2014-04-09 | GSE55080 | GEO
Project description:PRDM16 is an important transcriptional regulator of brown and beige adipocyte gene programs. We discovered that PRDM16 also represses type I Interferon-stimulated genes (ISGs) in brown and beige adipocytes. ChIP-seq demonstrated that PRDM16 binds proximal to many of the regulated ISGs and this correlates with reduction in the amount of the activating mark, H3K27Ac. Together this data shows PRDM16 represses ISG expression through direct binding at promoter regions to block transcription.
2017-04-10 | GSE86017 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-04-10 | GSE86018 | GEO
Project description:We systematically determined the extent to which APPBP2 loss stimulate beige adipocyte biogenesis in a PRDM16-dependent fashion. To this end, we ran RNA-seq analysis in adipocytes that lack APPBP2 and/or PRDM16. By overlapping the transcriptome data with published dataset of brown/beige fat (Chondronikola et al., 2016; Perdikari et al., 2018; Shinoda et al., 2015a), we found that APPBP2 loss significantly increased 72 genes whose expression was enriched in brown adipocytes relative to white fat. Among 72 brown/beige fat-enriched genes, we found that 90.28% (65/72 genes) of them were regulated in a PRDM16-dependent manner. The data suggest that PRDM16 is required for the majority, if not all, of APPBP2’s action on brown fat genes
2022-06-06 | GSE196699 | GEO
Project description:Sustained responses to transient stimuli are important for animals to survive and reproduce in their environment. However, the mechanisms that underlie altered responses to temporary shifts in abiotic factors, such as temperature, remain poorly understood. Here, we find that transient cold exposure leads to sustained transcriptional and metabolic adaptations in brown adipose tissue, which are critical for an improved thermogenic response to secondary cold encounter. Primary thermogenic challenge triggers the delayed induction of a lipid biosynthesis program even after cessation of the original stimulus, which protects from subsequent exposures. By combining single-nucleus RNA sequencing, spatial transcriptomics, and immunofluorescence imaging, we discover that this lipogenic response is carried out by a distinct subpopulation of brown adipocytes that is localized along the perimeter of classical Ucp1high brown adipocytes. The protective effect of the lipogenic program is associated with the production of acyl carnitines, and supplementation of acyl carnitines recapitulates improved secondary cold responses even in the absence of lipogenesis. Overall, our data highlight the importance of heterogenous brown adipocyte populations for “thermogenic memory” in the setting of repeated cold exposure, which may have implications for therapeutic efforts leveraging short-term thermogenesis to counteract the hypercaloric state of obesity.
2023-09-11 | GSE218709 | GEO
Project description:Brown adipose tissue (BAT) dissipates chemical energy in the form of heat, as a defense against hypothermia and obesity. Current evidence indicates that brown adipocytes arise from Myf5+-dermotomal precursors through the action of a PRDM16-C/EBP-_ transcriptional complex; however, the underlying mechanisms that determine lineage specification and maintenance of brown adipose cells remain poorly understood. Here we study the role of euchromatic histone-lysine N-methyltransferase 1 (EHMT1), a brown fat-enriched lysine methyltransferase, as an essential enzymatic component of the PRDM16 transcriptional complex and controls brown adipose cell fate. To identify targets and function of EHMT1, we performed genome-wide gene expression profiling of BAT from control mouce (Ehmt1flox/flox), Ehmt1Myf5 KO mouse (Myf5-Cre+/-; Ehmt1flox/flox) and Ehmt1adipo KO mouse (Adipo-Cre+/-; Ehmt1flox/flox). Loss of EHMT1 in Myf5+ lineage causes a near total loss of brown fat characteristics and induces muscle-selective gene program in vivo. In addition, adipose-specific deletion of EHMT1 by Adipo-Cre leads to a marked reduction of the thermogenic and fat oxidation genes.
2013-11-07 | E-MTAB-1704 | biostudies-arrayexpress
Project description:Brown adipose tissue (BAT) functions in energy expenditure in part due its role in thermoregulation. The prominent capacity of BAT to enhance fuel utilization and energy expenditure makes it an attractive target for treating obesity and metabolic disorders. Prolonged cold exposure induces de novo recruitment of brown adipocytes and activates their thermogenic activity. However, the exact source of cold-induced brown adipocytes is not completely understood. In this study, we sought to investigate the cellular origin of cold-induced brown adipocytes using single-cell RNA sequencing. We identified two distinct types of adipocyte progenitors that contribute to de novo recruitment of brown adipocytes in response to cold challenge. One is the previously known Pdgfra-expressing mesenchymal progenitors and the other is a vascular smooth muscle-derived adipocyte progenitor (VSM-APC) population, which expresses the temperature-sensitive ion channel transient receptor potential cation channel subfamily V member 1 (Trpv1). Using flow cytometry and lineage tracing, we demonstrated that the Trpv1pos VSM-APCs were indeed distinct from the Pdgfrapos progenitors and could contribute to brown adipocytes with greater thermogenic potential. Together, these findings illustrate a landscape of thermogenic adipose niche at the single cell resolution and identify a new cellular origin for the development of brown adipocytes.
2021-01-18 | GSE160585 | GEO