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

Tissue fibrosis is a serious complication of Crohn’s 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: Crohn’s 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.