Abstract
BackgroundNecrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation.MethodsUsing laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data.ResultsWe found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation.ConclusionsWe have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping.
Highlights
Necrotizing enterocolitis remains a leading cause of death in premature infants [1,2,3] for which there remain limited treatment options, no reliable biomarkers and theGood et al Clin Epigenet (2020) 12:190 some additional insights into the gene expression profiles of infants with surgical NEC, there is considerable variability in the samples
Albeit less pronounced, global differences when surgical NEC (sNEC) ileum was compared to non-NEC ileal samples with the exception that CpG islands (CGIs) shores and promoters showed little or no difference in the overall methylation level between sNEC and non-NEC ileal samples (Additional file 2: Figure S1B)
We identified CpG sites falling into low methylation (LM) (< 20%), intermediate methylation (IM) (20–80%) and high methylation (HM) (> 80%) categories and found that for both non-NEC ileum and nonNEC colon, approximately 2% of sites were categorized as LM with the remainder being distributed relatively evenly between IM and HM sites
Summary
Good et al Clin Epigenet (2020) 12:190 some additional insights into the gene expression profiles of infants with surgical NEC, there is considerable variability in the samples To combat this limitation, we developed the NEC biorepository [7, 8], which provides us with the unique opportunity to advance the field of NEC research with a larger number of samples for sequencing and analysis. We developed the NEC biorepository [7, 8], which provides us with the unique opportunity to advance the field of NEC research with a larger number of samples for sequencing and analysis These intestinal samples will help to further identify the precise molecular signaling pathways involved in the pathogenesis of sNEC, with the hope to identify infants at the highest risk for the development of this devastating disease. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call