RT Journal Article
T1 Genome-wide analysis of DNA methylation in Hirschsprung enteric precursor cells: unraveling the epigenetic landscape of enteric nervous system development
A1 Villalba-Benito, Leticia
A1 López-López, Daniel
A1 Torroglosa, Ana
A1 Casimiro-Soriguer, Carlos S.
A1 Luzón-Toro, Berta
A1 Fernández, Raquel María
A1 Moya-Jiménez, María José
A1 Antiñolo, Guillermo
A1 Dopazo, Joaquín
A1 Borrego, Salud
K1 Hirschsprung disease
K1 Whole genome bisulfte sequencing
K1 DNA methylation
K1 Enteric nervous system development
K1 Epigenetic regulation
K1 Neural crest
K1 CpG islands
K1 Genome
K1 Enfermedad de hirschsprung
K1 Secuenciación completa del genoma
K1 Metilación de ADN
K1 Sistema nervioso entérico
K1 Epigenómica
K1 Cresta neural
K1 Islas de CpG
K1 Genoma
AB BackgroundHirschsprung 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.ResultsThis 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.ConclusionsThis 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.
PB BioMed Central, Springer Nature
YR 2021
FD 2021-03-09
LK http://hdl.handle.net/10668/4394
UL http://hdl.handle.net/10668/4394
LA en
NO 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
DS RISalud
RD Apr 9, 2025