Genome-wide maps of chromatin state in human adipose derived stem cells isolated from abdominal (abd) and gluteofemoral (glut) subcutaneous adipose tissue
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. Overall design: Human adipose derived stem cells (hASC) isolated from abdominal (abd) and gluteofemoral (glut) 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