Dataset Information

Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine.

ABSTRACT: The reprogramming of cellular memory in specific cell types, and in visceral adipocytes in particular, appears to be a fundamental aspect of obesity and its related negative health outcomes. We explored the hypothesis that adipose tissue contains epigenetically distinct subpopulations of adipocytes that are differentially potentiated to record cellular memories of their environment. Adipocytes are large, fragile, and technically difficult to efficiently isolate and fractionate. We developed fluorescence nuclear cytometry (FNC) and fluorescence activated nuclear sorting (FANS) of cellular nuclei from visceral adipose tissue (VAT) using the levels of the pan-adipocyte protein, peroxisome proliferator-activated receptor gamma-2 (PPARg2), to distinguish classes of PPARg2-Positive (PPARg2-Pos) adipocyte nuclei from PPARg2-Negative (PPARg2-Neg) leukocyte and endothelial cell nuclei. PPARg2-Pos nuclei were 10-fold enriched for most adipocyte marker transcripts relative to PPARg2-Neg nuclei. PPARg2-Pos nuclei showed 2- to 50-fold higher levels of transcripts encoding most of the chromatin-remodeling factors assayed, which regulate the methylation of histones and DNA cytosine (e.g., DNMT1, TET1, TET2, KDM4A, KMT2C, SETDB1, PAXIP1, ARID1A, JMJD6, CARM1, and PRMT5). PPARg2-Pos nuclei were large with decondensed chromatin. TAB-seq demonstrated 5-hydroxymethylcytosine (5hmC) levels were remarkably dynamic in gene bodies of various classes of VAT nuclei, dropping 3.8-fold from the highest quintile of expressed genes to the lowest. In short, VAT-derived adipocytes appear to be more actively remodeling their chromatin than non-adipocytes.

SUBMITTER: Yu P

PROVIDER: S-EPMC4865362 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine.

Yu Ping P Ji Lexiang L Lee Kevin J KJ Yu Miao M He Chuan C Ambati Suresh S McKinney Elizabeth C EC Jackson Crystal C Baile Clifton A CA Schmitz Robert J RJ Meagher Richard B RB

PloS one 20160512 5

The reprogramming of cellular memory in specific cell types, and in visceral adipocytes in particular, appears to be a fundamental aspect of obesity and its related negative health outcomes. We explored the hypothesis that adipose tissue contains epigenetically distinct subpopulations of adipocytes that are differentially potentiated to record cellular memories of their environment. Adipocytes are large, fragile, and technically difficult to efficiently isolate and fractionate. We developed fluo ...[more]

PMID: 27171244

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Project description:Differences in the inherent properties of adipose tissue-derived stem cells (ASC) may contribute to the biological specificity of the subcutaneous (Sc) and visceral (V) adipose tissue depots. In this study, three distinct subpopulations of ASC, i.e. ASCSVF, ASCBottom, and ASCCeiling, were isolated from Sc and V fat biopsies of non-obese subjects, and their gene expression and functional characteristics were investigated. Genome-wide mRNA expression profiles of ASCSVF, ASCBottom and ASCCeiling from Sc fat were significantly different as compared to their homologous subsets of V-ASCs. Furthermore, ASCSVF, ASCCeiling and ASCBottom from the same fat depot were also distinct from each other. In this respect, both principal component analysis and hierarchical clusters analysis showed that ASCCeiling and ASCSVF shared a similar pattern of closely related genes, which was highly different when compared to that of ASCBottom. However, larger variations in gene expression were found in inter-depot than in intra-depot comparisons. The analysis of connectivity of genes differently expressed in each ASC subset demonstrated that, although there was some overlap, there was also a clear distinction between each Sc-ASC and their corresponding V-ASC subsets, and among ASCSVF, ASCBottom, and ASCCeiling of Sc or V fat depots in regard to networks associated with regulation of cell cycle, cell organization and development, inflammation and metabolic responses. Finally, the release of several cytokines and growth factors in the ASC cultured medium also showed both inter- and intra-depot differences. Thus, ASCCeiling and ASCBottom can be identified as two genetically and functionally heterogeneous ASC populations in addition to the ASCSVF, with ASCBottom showing the highest degree of unmatched gene expression. On the other hand, inter-depot seem to prevail over intra-depot differences in the ASC gene expression assets and network functions, contributing to the high degree of specificity of Sc and V adipose tissue in humans.

Dataset Information

Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine.

Publications

Subsets of Visceral Adipose Tissue Nuclei with Distinct Levels of 5-Hydroxymethylcytosine.

Similar Datasets

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