Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/4394
Title: Genome-wide analysis of DNA methylation in Hirschsprung enteric precursor cells: unraveling the epigenetic landscape of enteric nervous system development
Authors: Villalba-Benito, Leticia
López-López, Daniel
Torroglosa, Ana
Casimiro-Soriguer, Carlos S.
Luzón-Toro, Berta
Fernández, Raquel María
Moya-Jiménez, María José
Antiñolo, Guillermo
Dopazo, Joaquín
Borrego, Salud
metadata.dc.contributor.authoraffiliation: [Villalba-Benito,L; Torroglosa,A; Luzón-Toro,B; Fernández,RM; Antiñolo,G; Dopazo,J; Borrego,S] Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. [Villalba-Benito,L; Torroglosa,A; Luzón-Toro,B; Fernández,RM; Antiñolo,G; Dopazo,J; Borrego,S] Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. [López-López,D; Casimiro-Soriguer,CS; Dopazo,J] Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), CDCA, University Hospital Virgen del Rocío, Sevilla, Spain. [López-López,D; Casimiro-Soriguer,CS; Dopazo,J] Computational Systems Medicine, IBIS, University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. [Moya-Jiménez,MJ] Department of Pediatric Surgery, University Hospital Virgen del Rocío, Seville, Spain.
Keywords: Hirschsprung disease;Whole genome bisulfte sequencing;DNA methylation;Enteric nervous system development;Epigenetic regulation;Neural crest;CpG islands;Genome;Enfermedad de hirschsprung;Secuenciación completa del genoma;Metilación de ADN;Sistema nervioso entérico;Epigenómica;Cresta neural;Islas de CpG;Genoma
metadata.dc.subject.mesh: Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies
Medical Subject Headings::Persons::Persons::Age Groups::Child::Child, Preschool
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::GC Rich Sequence::CpG Islands
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomics
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome
Medical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Digestive System Abnormalities::Hirschsprung Disease
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Persons::Persons::Age Groups::Infant
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Anatomy::Embryonic Structures::Neural Crest
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Motivation::Goals
Medical Subject Headings::Anatomy::Nervous System::Peripheral Nervous System::Autonomic Nervous System::Enteric Nervous System
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation
Medical Subject Headings::Information Science::Information Science::Information Storage and Retrieval::Databases as Topic::Databases, Factual::Databases, Genetic
Issue Date: 9-Mar-2021
Publisher: BioMed Central, Springer Nature
Citation: Villalba-Benito L, López-López D, Torroglosa A, Casimiro-Soriguer CS, Luzón-Toro B, Fernández RM, et al. Genome-wide analysis of DNA methylation in Hirschsprung enteric precursor cells: unraveling the epigenetic landscape of enteric nervous system development. Clin Epigenetics. 2021 Mar 9;13(1):51
Abstract: Background Hirschsprung disease (HSCR, OMIM 142623) is a rare congenital disorder that results from a failure to fully colonize the gut by enteric precursor cells (EPCs) derived from the neural crest. Such incomplete gut colonization is due to alterations in EPCs proliferation, survival, migration and/or differentiation during enteric nervous system (ENS) development. This complex process is regulated by a network of signaling pathways that is orchestrated by genetic and epigenetic factors, and therefore alterations at these levels can lead to the onset of neurocristopathies such as HSCR. The goal of this study is to broaden our knowledge of the role of epigenetic mechanisms in the disease context, specifically in DNA methylation. Therefore, with this aim, a Whole-Genome Bisulfite Sequencing assay has been performed using EPCs from HSCR patients and human controls. Results This is the first study to present a whole genome DNA methylation profile in HSCR and reveal a decrease of global DNA methylation in CpG context in HSCR patients compared with controls, which correlates with a greater hypomethylation of the differentially methylated regions (DMRs) identified. These results agree with the de novo Methyltransferase 3b downregulation in EPCs from HSCR patients compared to controls, and with the decrease in the global DNA methylation level previously described by our group. Through the comparative analysis of DMRs between HSCR patients and controls, a set of new genes has been identified as potential susceptibility genes for HSCR at an epigenetic level. Moreover, previous differentially methylated genes related to HSCR have been found, which validates our approach. Conclusions This study highlights the relevance of an adequate methylation pattern for a proper ENS development. This is a research area that provides a novel approach to deepen our understanding of the etiopathogenesis of HSCR.
URI: http://hdl.handle.net/10668/4394
metadata.dc.relation.publisherversion: https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-021-01040-6
metadata.dc.identifier.doi: 10.1186/s13148-021-01040-6
ISSN: 1868-7083 (Online)
Appears in Collections:01- Artículos - FPS. Fundación Pública Andaluza Progreso y Salud
01- Artículos - Hospital Virgen del Rocío
01- Artículos - IBIS. Instituto de Biomedicina de Sevilla

Files in This Item:
File Description SizeFormat 
VillalbaBenito_GenomeWideAnalysis.pdfArtículo publicado3,85 MBAdobe PDFView/Open
VillalbaBenito_GenomeWideAnalysis_MaterialSuplementario_1.pdfMaterial suplementario99,12 kBAdobe PDFView/Open
VillalbaBenito_GenomeWideAnalysis_MaterialSuplementario_2.xlsxMaterial suplementario250,13 kBMicrosoft Excel XMLView/Open
VillalbaBenito_GenomeWideAnalysis_MaterialSuplementario_3.pdfMaterial suplementario188,69 kBAdobe PDFView/Open
VillalbaBenito_GenomeWideAnalysis_MaterialSuplementario_4.xlsxMaterial suplementario139,7 kBMicrosoft Excel XMLView/Open
VillalbaBenito_GenomeWideAnalysis_MaterialSuplementario_5.xlsxMaterial suplementario36,8 kBMicrosoft Excel XMLView/Open
VillalbaBenito_GenomeWideAnalysis_MaterialSuplementario_6.pdfMaterial suplementario53,14 kBAdobe PDFView/Open


This item is protected by original copyright



This item is licensed under a Creative Commons License Creative Commons