Author, as appears in the article.: Serena C; Millan M; Ejarque M; Saera-Vila A; Maymó-Masip E; Núñez-Roa C; Monfort-Ferré D; Terrón-Puig M; Bautista M; Menacho M; Martí M; Espin E; Vendrell J; Fernández-Veledo S
Department: Bioquímica i Biotecnologia Medicina i Cirurgia
URV's Author/s: Fernandez Veledo, Sonia / Maymo Masip, Elsa / Monfort Ferre, Diandra / Serena Perelló, Carolina / Terrón Puig, Margarida Maria / Vendrell Ortega, Juan José
Keywords: Tissue Regulators Profile Obesity Normalization Methylome Inflammatory bowel disease Inflammation Immune properties Gene-expression Gene expression Epigenetics Differentiation Bone-marrow Adipose tissue inflammatory bowel disease gene expression epigenetics adipose tissue
Abstract: BACKGROUND: Crohn's disease (CD) is characterized by persistent inflammation and ulceration of the small or large bowel, and expansion of mesenteric adipose tissue, termed creeping fat (CF). We previously demonstrated that human adipose-derived stem cells (hASCs) from CF of patients with CD exhibit dysfunctional phenotypes, including a pro-inflammatory profile, high phagocytic capacity, and weak immunosuppressive properties. Importantly, these phenotypes persist in patients in remission and are found in all adipose depots explored including subcutaneous fat. We hypothesized that changes in hASCs are a consequence of epigenetic modifications. METHODS: We applied epigenome-wide profiling with a methylation array (Illumina EPIC/850k array) and gene expression analysis to explore the impact of CD on the methylation signature of hASCs isolated from the subcutaneous fat of patients with CD and healthy controls (n = 7 and 5, respectively; cohort I). Differentially methylated positions (p value cutoff < 1 × 10-4 and ten or more DMPs per gene) and regions (inclusion threshold 0.2, p value cutoff < 1 × 10-2 and more than 2 DMRs per gene) were identified using dmpfinder and Bumphunter (minfi), respectively. Changes in the expression of differentially methylated genes in hASCs were validated in a second cohort (n = 10/10 inactive and active CD and 10 controls; including patients from cohort I) and also in peripheral blood mononuclear cells (PBMCs) of patients with active/inactive CD and of healthy controls (cohort III; n = 30 independent subjects). RESULTS: We found a distinct DNA methylation landscape in hASCs from patients with CD, leading to changes in the expression of differentially methylated genes involved in immune response, metabolic, cell differentiation, and development processes. Notably, the expression of several of these genes in hASCs and PBMCs such as tumor necrosis factor alpha (TNFA) and PR domain zinc finger protein 16 (PRDM16) were not restored to normal (healthy) levels after disease remission. CONCLUSIONS: hASCs of patients with CD exhibit a unique DNA methylation and gene expression profile, but the expression of several genes are only partially restored in patients with inactive CD, both in hASCs and PBMCs. Understanding how CD shapes the functionality of hASCs is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies. Human adipose-stem cells isolated from subcutaneous fat of patients with Crohn's disease exhibit an altered DNA methylation pattern and gene expression profile compared with those isolated from healthy individuals, with immune system, cell differentiation, metabolic and development processes identified as the main pathways affected. Interestingly, the gene expression of several genes involved in these pathways is only partially restored to control levels in patients with inactive Crohn's disease, both in human adipose-stem cells and peripheral blood mononuclear cells. Understanding how Crohn's disease shapes the functionality of human adipose-stem cells is critical for investigating the complex pathophysiology of this disease, as well as for the success of cell-based therapies.
Thematic Areas: Oncology Odontología Molecular biology Medicina i Genetics (clinical) Genetics & heredity Genetics General medicine Developmental biology Ciências biológicas ii Ciências biológicas i Biotecnología
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 18687075
Author's mail: carolina.serena@urv.cat elsa.maymo@urv.cat diandra.monfort@estudiants.urv.cat margaridamaria.terron@estudiants.urv.cat sonia.fernandez@urv.cat jvortega@iispv.cat
Author identifier: 0000-0002-9133-3120 0000-0003-3832-4249 0000-0003-2906-3788 0000-0002-6994-6115
Record's date: 2024-12-14
Papper version: info:eu-repo/semantics/publishedVersion
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Clinical Epigenetics. 12 (1): 53-
APA: Serena C; Millan M; Ejarque M; Saera-Vila A; Maymó-Masip E; Núñez-Roa C; Monfort-Ferré D; Terrón-Puig M; Bautista M; Menacho M; Martí M; Espin E; Vend (2020). Adipose stem cells from patients with Crohn's disease show a distinctive DNA methylation pattern. Clinical Epigenetics, 12(1), 53-. DOI: 10.1186/s13148-020-00843-3
Entity: Universitat Rovira i Virgili
Journal publication year: 2020
Publication Type: Journal Publications
Repositori URV