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Developmental origins define epigenomic differences between subcutaneous and visceral adipocytes [Bisulfite-Seq]

ABSTRACT: Developmental origins define epigenomic differences between subcutaneous and visceral adipocytes [Bisulfite-Seq]

PROVIDER: PRJNA437062 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6808730_1.fastq.gz	Fastqsanger.gz
	SRR6808730_2.fastq.gz	Fastqsanger.gz
	SRR6808731_1.fastq.gz	Fastqsanger.gz
	SRR6808731_2.fastq.gz	Fastqsanger.gz
	SRR6808722_1.fastq.gz	Fastqsanger.gz

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Developmental origins define epigenomic differences between subcutaneous and visceral adipocytes

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Project description:Obesity is characterized by the excess of body fat leading to impaired health. Abdominal fat is particularly harmful and is associated with cardiovascular and metabolic diseases and cancer. In contrast, subcutaneous fat is generally considered less detrimental. The mechanisms that establish the cellular characteristics of these distinct fat types in humans are not fully understood. Here, we explored whether differences of their gene regulatory mechanisms can be investigated in vitro. For this purpose, we in vitro differentiated human visceral and subcutaneous pre-adipocytes into mature adipocytes and obtained their gene expression profiles and genome-wide H3K4me3, H3K9me3 and H3K27ac patterns. Subsequently, we compared those data with public gene expression data from visceral and subcutaneous fat tissues. We found that the in vitro differentiated adipocytes show significant differences in their transcriptional landscapes, which correlate with biological pathways that are characteristic for visceral and subcutaneous fat tissues, respectively. Unexpectedly, visceral adipocyte enhancers are rich on motifs for transcription factors involved in the Hippo-YAP pathway, cell growth and inflammation, which are not typically associated with adipocyte function. In contrast, enhancers of subcutaneous adipocytes show enrichment of motifs for common adipogenic transcription factors, such as C/EBP, NFI and PPARgamma, implicating substantially disparate gene regulatory networks in visceral and subcutaneous adipocytes. Consistent with the role in obesity, predominantly the histone modification pattern of visceral adipocytes is linked to obesity-associated diseases. Thus, this work suggests that the properties of visceral and subcutaneous fat tissues can be studied in vitro and provides preliminary insights into their gene regulatory processes.

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Comparative proteomics of human visceral and subcutaneous adipocytes

Project description:Adipose tissue (AT) distribution is an important determinant of cardiometabolic health. Increased visceral adiposity has been associated with a higher risk of obesity-related diseases. An important step in deciphering the molecular complexity of subcutaneous AT (SAT) and visceral AT (VAT) is to elucidate the molecular composition of the principal AT cell type, adipocytes. We present a comprehensive protein expression profile of abdominal subcutaneous (SA) and omental visceral adipocytes (VA). We isolated adipocytes from paired AT biopsies obtained during bariatric surgery of 19 morbidly obese women (BMI > 30 kg/m2) and performed state-of-the-art mass spectrometry to investigate their proteome profiles. We identified 3,686 proteins groups and found 1,140 differentially expressed proteins (adj. p-value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. In addition to providing a global protein profile of abdominal SA and omental VA, we also present the most differentially expressed pathways and processes distinguishing SA from VA. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and also to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA. We also performed prediction analyses of differentially expressed putative secreted proteins, which revealed a significantly higher number of potentially secreted proteins in SA compared to VA. Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity. Additionally, we predict possible protein targets among secreted proteins, which may be utilized for the further investigation of the role of different AT depots in obesity using peripheral blood.

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Developmental origins define epigenomic differences between subcutaneous and visceral adipocytes [RNA_seq_Whole]

Project description:To understand the molecular differences between adipocytes and their contribution to cell-type specific function, we comprehensively characterised the transcriptomes and DNA methylomes using WGBS of isolated adipocytes from the SAT and VAT from normal weight individuals

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