Genome-wide analysis of DNA methylation in Hirschsprung enteric precursor cells: unraveling the epigenetic landscape of enteric nervous system development
| Autor: | Joaquín Dopazo, Leticia Villalba-Benito, Berta Luzón-Toro, Raquel M. Fernández, Salud Borrego, Daniel Lopez-Lopez, María José Moya-Jiménez, Carlos S. Casimiro-Soriguer, Guillermo Antiñolo, Ana Torroglosa |
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| Přispěvatelé: | Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Universidad de Sevilla. Departamento de Cirugía, [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, 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, 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., This work was supported by Instituto de Salud Carlos III through the Projects [PI16/0142, PI19/01550] (co-funded by the European Regional Development Fund/European Social Fund, 'A way to make Europe'/'Investing in your future'), and by the Regional Ministry of Health and Family of the Regional Government of Andalusia [PEER-0470–2019]. L.V.-B. was supported by a fellowship associated with the CTS-7447 Project, which has been funded by the Regional Ministry of Innovation, Science and Enterprise of the Regional Government of Andalusia. |
| Rok vydání: | 2021 |
| Předmět: |
Epigenomics
Male Methyltransferase Hirschsprung disease Bisulfite sequencing Whole genome bisulfite sequencing Enteric Nervous System Epigenesis Genetic Secuenciación completa del genoma Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Phenomena and Processes::Genetic Phenomena::Genetic Processes::DNA Methylation [Medical Subject Headings] Anatomy::Nervous System::Peripheral Nervous System::Autonomic Nervous System::Enteric Nervous System [Medical Subject Headings] Enfermedad de hirschsprung Genetics (clinical) Genetics Persons::Persons::Age Groups::Infant [Medical Subject Headings] Genome DNA methylation Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings] Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::GC Rich Sequence::CpG Islands [Medical Subject Headings] Enteric nervous system development Diseases::Congenital Hereditary and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Digestive System Abnormalities::Hirschsprung Disease [Medical Subject Headings] Methylation Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings] Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomics [Medical Subject Headings] CpG site Neural Crest Child Preschool Cresta neural Female Metilación de ADN Signal Transduction Islas de CpG Check Tags::Male [Medical Subject Headings] Context (language use) Biology Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome [Medical Subject Headings] Epigenetic regulation Whole genome bisulfte sequencing Psychiatry and Psychology::Behavior and Behavior Mechanisms::Motivation::Goals [Medical Subject Headings] Information Science::Information Science::Information Storage and Retrieval::Databases as Topic::Databases Factual::Databases Genetic [Medical Subject Headings] Humans Genetic Predisposition to Disease Epigenetics Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings] Molecular Biology Genoma Whole Genome Sequencing Anatomy::Embryonic Structures::Neural Crest [Medical Subject Headings] Research Sistema nervioso entérico Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis Genetic [Medical Subject Headings] Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction [Medical Subject Headings] Infant Differentially methylated regions Check Tags::Female [Medical Subject Headings] Case-Control Studies Epigenómica CpG Islands Persons::Persons::Age Groups::Child::Child Preschool [Medical Subject Headings] Developmental Biology |
| Zdroj: | Clinical Epigenetics Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | [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. This work was supported by Instituto de Salud Carlos III through the Projects [PI16/0142, PI19/01550] (co-funded by the European Regional Development Fund/European Social Fund, "A way to make Europe"/"Investing in your future"); and by the Regional Ministry of Health and Family of the Regional Government of Andalusia [PEER-0470–2019]. L.V.-B. was supported by a fellowship associated with the CTS-7447 Project, which has been funded by the Regional Ministry of Innovation, Science and Enterprise of the Regional Government of Andalusia. |
| Databáze: | OpenAIRE |
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