Transcriptomic Characterization of Human Beige Adipocyte Differentiated From Adipose Mesenchymal Stem Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE125331 | GEO | 2020/01/01
REPOSITORIES: GEO
Similar Datasets
Project description:Two types of UCP1 positive cells-brown and beige adipocytes exist in mammals. Beige adipocytes are very plastic, and can be dynamically regulated by environment.Beige adipocytes formed postnatally in subcutaneous inguinal white adipose tissue (iWAT) lost thermogenic gene expression and multilocular morphology at adult stage, but cold could restore their “beigeing” characteristics, a phenomenon termed as beige adipocyte renaissance. Our results showed that beige cell maintenance and renaissance in adult mice were regulated by cAMP and HDAC4 signaling in white adipocytes non-cell autonomously. Genetic modulations of various components of this cAMP-HDAC4 cascade (e.g. LKB1) led to persistent browning and reduced adiposity independent of thermogenesis. To further study the mechanisms of beige adipocytes maintenance, we performed RNA-seq with samples from inguinal white adipose tissues of WT, AdipoqCre LKB1 F/F, and AdipoqCre LKB1 F/F; HDAC4 F/F mice.Our studies will move the beige adipocyte field forward and attract clinical applications to target beige adipocyte renaissance.
2018-02-14 | GSE85335 | GEO
Project description:Beige and brown adipocytes generate heat in response to reductions in ambient temperature. When warmed, both beige and brown adipocytes exhibit morphological ‘whitening’, but it is unknown whether or to what extent this represents a true shift in cellular identity. Using cell type-specific profiling in vivo, we uncover a unique paradigm of temperature-dependent epigenomic plasticity of beige, but not brown, adipocytes, with conversion from a brown to a white chromatin state. Despite this profound shift in cellular identity, warm whitened beige adipocytes retain an epigenomic memory of prior cold exposure defined by an array of poised enhancers that prime thermogenic genes for rapid response during a second bout of cold exposure. We further show that a transcriptional cascade involving the glucocorticoid receptor and Zfp423 can drive warm-induced whitening of beige adipocytes. These studies identify the epigenomic and transcriptional bases of an extraordinary example of cellular plasticity in response to environmental signals.
2018-03-01 | GSE108077 | GEO
Project description:Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression in brown and beige adipocytes and that SUV420H2 knockdown significantly reduces, whereas SUV420H2 overexpression significantly increases UCP1 levels in brown adipocytes. Suv420h2 knockout (H2KO mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study showed that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) promoter, leading to down-regulated expression of 4E-BP1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.
2024-05-09 | GSE244457 | GEO
Project description:Background: The beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes. Methods: We performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects, and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing. Results: We find 693 exon junctions with robust differential usage between white and beige adipocytes in all 6 subjects, mapping to 507 genes. Importantly, only 8% of these differentially spliced genes are also differentially expressed, indicating that alternative splicing constitutes an additional layer of gene expression regulation during beige adipocyte adipogenic differentiation. Functional classification of alternative isoforms point to a gain of function for key thermogenic regulators such as PPARG, CITED1 and PEMT. We find that a large majority of the splice variants arise from differential usage of transcription start sites (TSSs), with beige-specific TSSs being enriched for PPARγ and MED1 binding compared to white-specific TSSs. Finally, we validate beige specific isoform expression at the protein level for two thermogenic regulators, PPARγ and PEMT. Discussion: These results indicate that differential isoform expression through alternative TSS usage is an important regulatory mechanism for human adipocyte thermogenic specification.
2024-05-14 | GSE256260 | GEO
Project description:Background: The beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes. Methods: We performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects, and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing. Results: We find 693 exon junctions with robust differential usage between white and beige adipocytes in all 6 subjects, mapping to 507 genes. Importantly, only 8% of these differentially spliced genes are also differentially expressed, indicating that alternative splicing constitutes an additional layer of gene expression regulation during beige adipocyte adipogenic differentiation. Functional classification of alternative isoforms point to a gain of function for key thermogenic regulators such as PPARG, CITED1 and PEMT. We find that a large majority of the splice variants arise from differential usage of transcription start sites (TSSs), with beige-specific TSSs being enriched for PPARγ and MED1 binding compared to white-specific TSSs. Finally, we validate beige specific isoform expression at the protein level for two thermogenic regulators, PPARγ and PEMT. Discussion: These results indicate that differential isoform expression through alternative TSS usage is an important regulatory mechanism for human adipocyte thermogenic specification. Code for data processing and analysis are available at https://github.com/sarahhp/splicing_thermogenesis.
2024-05-14 | GSE256259 | GEO
Project description:We found deletion of Foxp4 in mature adipocytes would augment juvenile and mature beige adipocyte thermogenesis.In order to investage the binding site of Foxp4 in the genome of beige adipocytes, we did Foxp4 ChIP-Seq with differentiated SVF cells derived from ingunal adipose tissues.
2022-04-06 | GSE199559 | GEO
Project description:Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression in brown and beige adipocytes and that SUV420H2 knockdown significantly reduces, whereas SUV420H2 overexpression significantly increases UCP1 levels in brown adipocytes. Suv420h2 knockout (H2KO mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study showed that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) promoter, leading to down-regulated expression of 4E-BP1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.
2024-05-09 | GSE245509 | GEO
Project description:Prolonged cold exposure stimulates the recruitment of beige adipocytes within white adipose tissue. Beige adipocytes depend on mitochondrial oxidative phosphorylation to drive thermogenesis. The transcriptional mechanisms that promote remodeling in adipose tissue during the cold are not well understood. Here we demonstrate that the transcriptional coregulator transducin-like enhancer of split 3 (TLE3) inhibits mitochondrial gene expression in beige adipocytes. Conditional deletion of TLE3 in adipocytes promotes mitochondrial oxidative metabolism and increases energy expenditure, thereby improving glucose control. Using chromatin immunoprecipitation and deep sequencing, we found that TLE3 occupies distal enhancers in proximity to nuclear-encoded mitochondrial genes and that many of these binding sites are also enriched for early B-cell factor (EBF) transcription factors. TLE3 interacts with EBF2 and blocks its ability to promote the thermogenic transcriptional program. Collectively, these studies demonstrate that TLE3 regulates thermogenic gene expression in beige adipocytes through inhibition of EBF2 transcriptional activity. Inhibition of TLE3 may provide a novel therapeutic approach for obesity and diabetes.
2019-05-23 | GSE116767 | GEO
Project description:Beige adipocytes accumulates mitochondria and alleviates metabolic disorder via activating energy expenditure. Whether the opposing process of mitochondrial biogenesis and clearance are integrated regulated in beige adipocytes is beyond known. Here we show that DNA binding protein Ets1 suppresses beige adipocyte formation via bidirectional regulation of mitochondrial biogenesis and clearance. The expression level of Ets1 was down-regulated in browning adipocytes, and up-regulated in the subcutaneous fat of obese mice. Adipocyte Ets1 heterozygous knock-in mice showed suppressed beige adipocytes formation under cold stress, while the homozygous knock-in mice are cold intolerance. On the other hand, knocking out Ets1 in adipocytes enhanced energy expenditure and protect the mice from high fat diet induced metabolic disorders. Mechanical assay suggests Ets1 binds to the promoter region of mitochondria complex coding genes and autophagy related genes, transcriptionally suppresses mitochondrial biogenesis and activates its clearance. Our results indicate that Ets1 integrally regulates the balance of mitochondria generation and degradation, hence acts as a pivotal governor of mitochondria content and negatively regulates beige adipocyte formation.
2023-07-01 | GSE234879 | GEO
Project description:Alternative isoform expression of key thermogenic genes in human beige adipocytes
| PRJNA1078799 | ENA