RNA-seq analysis of abdominal and gulteofemoral adipose derived stem cells isolated form PCOS and control women
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE193812 | GEO | 2022/03/09
REPOSITORIES: GEO
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Project description:In vitro studies of subcutaneous (SC) abdominal adipose stem cells (ASC) from women with polycystic ovary syndrome (PCOS) show altered ASC commitment to preadipocytes and differentiation to mature adipocytes related to hyperandrogenism. The goal of the study is to use microarrays to examine whether SC abdominal ASC gene expression are altered in normal-weight PCOS women and correlated with hyperandrogenemia and/or insulin resistance, which are prevalent clinical pathologies of PCOS.
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Project description:Over the past two decades, studies have identified distinct transcriptional signatures between ABD and GF-adipose tissues and between both body shapes. Remarkably, a significant fraction of these depot specific gene expression patterns and more recently the differential chromatin structure profiles have been shown to be conserved during the culture and in vitro differentiation of the precursor cells into mature adipocytes. Our team and others have also shown distinct DNA methylation levels between ABD and GF-AT, that are preserved in isolated ADSCs cultured in vitro. Altogether, these data suggest that depot specific epigenomic profiles contribute significantly to the unique transcriptional profiles of ABD vs GF adipose tissues depots. To extend these earlier studies and to determine how the differential gene expression patterns in different adipose depots may be significantly influenced by chromatin landscape we performed H3K4me3, H3K4me2, H3K27me3, H3K9me3 and CTCF ChIP-seq and ATAC-seq on chromatin isolated from ABD and GF-ADSCs. We paired this with highly differentially expressed genes between ABD and GF-ADSCs. Then, to evaluate the potential role for long range chromatin interactions we utilized an H3K27Ac Hi-ChIP approach to capture putative regulatory loops with at least one anchor being marked by this enhancer associated histone mark. This in-depth analysis of the chromatin structure and organization of ABD and GF-ADSCs provides a better understanding of the intrinsic genomic regulatory features that help define the functionally distinct phenotypes of different subcutaneous adipose tissue depots and how they influence fat distribution in women.
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Project description:Over the past two decades, studies have identified distinct transcriptional signatures between ABD and GF-adipose tissues and between both body shapes. Remarkably, a significant fraction of these depot specific gene expression patterns and more recently the differential chromatin structure profiles have been shown to be conserved during the culture and in vitro differentiation of the precursor cells into mature adipocytes. Our team and others have also shown distinct DNA methylation levels between ABD and GF-AT, that are preserved in isolated ADSCs cultured in vitro. Altogether, these data suggest that depot specific epigenomic profiles contribute significantly to the unique transcriptional profiles of ABD vs GF adipose tissues depots. To extend these earlier studies and to determine how the differential gene expression patterns in different adipose depots may be significantly influenced by chromatin landscape we performed H3K4me3, H3K4me2, H3K27me3, H3K9me3 and CTCF ChIP-seq and ATAC-seq on chromatin isolated from ABD and GF-ADSCs. We paired this with highly differentially expressed genes between ABD and GF-ADSCs. Then, to evaluate the potential role for long range chromatin interactions we utilized an H3K27Ac Hi-ChIP approach to capture putative regulatory loops with at least one anchor being marked by this enhancer associated histone mark. This in-depth analysis of the chromatin structure and organization of ABD and GF-ADSCs provides a better understanding of the intrinsic genomic regulatory features that help define the functionally distinct phenotypes of different subcutaneous adipose tissue depots and how they influence fat distribution in women.
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Project description:To identify the altered miRNA expression profiles of PCOS patients, the differentially expressed miRNAs were identified from cumulus cells of PCOS patients by comparing to that of normal women. Case-control study that involved 18 women with PCOS and 18 women without PCOS (control). The miRNA expression profiles of cumulus cells were identified by miRNA array.
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Project description:Why ~70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR), above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT), remains a fundamental question. In these experiments, we sought to explore the role of miRNAs in the AT of PCOS and matched controls. Analysis determined that PCOS AT has a differentially expressed miRNA profile, including upregulated miR-93. We observed a significant association between HOMA-IR, and GLUT4 and miR-93 expression in human AT. Our results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93, and demonstrate upregulated miR-93 expression in PCOS, possibly accounting for the IR of the syndrome, and also in non-PCOS women with IR. We performed miRNA microarrays to determine PCOS-related miRNA expression in adipose derived from lean PCOS patients and matched control women. We analyized miRNA from total RNA extracted from subcutaneous (sc) adipose tissue from three lean PCOS patients and three matched control women.
2012-09-06 | E-GEOD-37914 | biostudies-arrayexpress
Project description:Polycystic ovary syndrome (PCOS) is the most common endocrinological disorder of fertile-aged women. PCOS has been associated with adverse pregnancy outcomes and abnormalities of the placenta. By taking a quantitative label-free quantitative proteomics approach we set out to investigate if changes in the plasma proteome of pregnant women with PCOS could elucidate the mechanisms behind the pathologies observed in PCOS pregnancies. We have performed label-free quantitative proteomics on plasma samples from pregnant women with PCOS at term (n=14) and plasma samples from pregnant control women (n = 23) matched for age, gestational length and BMI. The samples are derived from BASIC pregnancy cohort from Uppsala, Sweden. A total of 169 proteins with two or more unique peptides were identified.
2019-11-25 | PXD012034 | Pride
Project description:Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting women of reproductive age. The main features of PCOS are hyperandrogenism and irregular menstrual cycles together with metabolic dysfunctions including abdominal obesity, dyslipidemia and an increased risk of developing type 2 diabetes. Despite the high prevalence of >15%, the pathophysiology of the syndrome is unclear. Gene expression array data from skeletal muscle and adipose tissue have provided some information about dysregulated metabolic pathways in women with PCOS, but the transcriptomic data need to be verified by proteomics to advance our understanding of PCOS. Skeletal muscle and adipose tissue biopsies from 10 women with PCOS and 10 controls were subjected to global proteomic analysis. Protein expression differences between cases and controls were based on Student’s t-test and corrected for multiple testing. In total, we identified 5000 proteins in adipose tissue and 3480 proteins in skeletal muscle. After correction for multiple testing, 74 proteins with q < 0.05 corresponding to 72 unique proteins were found to be differentially expressed in adipose tissue from women with PCOS versus controls. And, 123 proteins with q < 0.05 corresponding to 120 unique proteins were found to be differentially expressed in skeletal muscle from women with PCOS versus control. We then applied pathway analysis to the total protein and phosphopeptide data using PRISM and Enrichr.
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Project description:Human adipose serived stem cells (ASC) isolated from A and GF adipose tissue obtained from premenopausal women were used to perform assess accessible chromatin regions by ATAC-seq, chromatin marks, CTCF and RNAPII identification by chIP-seq
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Project description:Why ~70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR), above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT), remains a fundamental question. In these experiments, we sought to explore the role of miRNAs in the AT of PCOS and matched controls. Analysis determined that PCOS AT has a differentially expressed miRNA profile, including upregulated miR-93. We observed a significant association between HOMA-IR, and GLUT4 and miR-93 expression in human AT. Our results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93, and demonstrate upregulated miR-93 expression in PCOS, possibly accounting for the IR of the syndrome, and also in non-PCOS women with IR. We performed miRNA microarrays to determine PCOS-related miRNA expression in adipose derived from lean PCOS patients and matched control women.
2012-09-06 | GSE37914 | GEO
Project description:To identify the altered miRNA expression profiles of PCOS patients, the differentially expressed miRNAs were identified from cumulus cells of PCOS patients by comparing to that of normal women.
2016-06-01 | GSE72274 | GEO