Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Integration of genome-wide DNA methylome and transcriptome of human intestinal fibroblasts reveals novel candidate gene signatures in Crohnâs disease-associated fibrosis

ABSTRACT: Tissue fibrosis is a serious complication of Crohnâs disease (CD) as well as of a variety of other complex, chronic pathologies. Understanding the underlying pathophysiology of tissue fibrosis is crucial for the development of tissue-specific prevention and interventional treatment strategies. To identify molecular states specific to fibrotic disease, we employed deep sequencing to define the genome-wide DNA methylome and the whole transcriptome of purified human intestinal fibrotic fibroblasts (HIFs) isolated from the colon of patients with fibrotic CD. Integration of this information, via computational tools, identified candidate molecular interactions that could lead to fibrosis pathology. Our definition of a genome-wide fibrosis-specific DNA methylome provides a new paradigm for understanding mechanisms of pathological gene expression that lead to intestinal fibrosis and may have relevance to fibrogenesis in other organs. Human intestinal fibroblasts (HIFs) were extracted and cultured from colon specimens of two groups: Crohnâs disease with associated fibrosis (n=3) and normal fibroblasts from patients with Diverticulitis (n=3). Both RNA-seq and MBD-isolated genome sequencing (MiGS) were performed on every sample.

ORGANISM(S): Homo sapiens

SUBMITTER: Jeffrey Bhasin

PROVIDER: E-GEOD-67250 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide analysis of DNA methylation and gene expression defines molecular characteristics of Crohn's disease-associated fibrosis.

Sadler Tammy T Bhasin Jeffrey M JM Xu Yaomin Y Barnholz-Sloan Jill J Chen Yanwen Y Ting Angela H AH Stylianou Eleni E

Clinical epigenetics 20160312

<h4>Background</h4>Fibrosis of the intestine is a common and poorly understood complication of Crohn's disease (CD) characterized by excessive deposition of extracellular matrix and accompanied by narrowing and obstruction of the gut lumen. Defining the molecular characteristics of this fibrotic disorder is a vital step in the development of specific prediction, prevention, and treatment strategies. Previous epigenetic studies indicate that alterations in DNA methylation could explain the mechan ...[more]

PMID: 26973718

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Project description:Dupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD. In this study, we used primary cultures of fibroblasts derived from excisional biopsies of fibrotic tissue from DD patients to compare the gene expression profiles on a genome-wide basis with normal control fibroblasts. Our investigations have identified genes that may be involved with DD pathogenesis including some which are directly relevant to fibrosis. In particular, these include significantly reduced expression levels of three matrix metallopeptidases (MMP1, MMP3, MMP16), follistatin, and STAT1, and significantly increased expression levels of fibroblast growth factors (FGF9, FGF11), a number of collagen genes and other ECM genes in DD patient samples. Many of these gene products are known to be involved in fibrosis, tumour formation and in the normal processes of tissue remodelling. In addition, alternative splicing was identified in some DD-associated genes. These highly sensitive genomic investigations provide new insight into the molecular mechanisms that may underpin the development and progression of DD. Four exon arrays of DD primary fibroblasts derived from fibrotic tissue were compared to fibroblasts derived from skin punch biopsies from individuals who did not show DD symptoms.

Dataset Information

Integration of genome-wide DNA methylome and transcriptome of human intestinal fibroblasts reveals novel candidate gene signatures in Crohnâs disease-associated fibrosis

Publications

Genome-wide analysis of DNA methylation and gene expression defines molecular characteristics of Crohn's disease-associated fibrosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Integration of genome-wide DNA methylome and transcriptome of human intestinal fibroblasts reveals novel candidate gene signatures in Crohnâs disease-associated fibrosis

Publications

Genome-wide analysis of DNA methylation and gene expression defines molecular characteristics of Crohn's disease-associated fibrosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Integration of genome-wide DNA methylome and transcriptome of human intestinal fibroblasts reveals novel candidate gene signatures in Crohnâs disease-associated fibrosis