DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome

Howell, Kate J.; Kraiczy, Judith; Nayak, Komal; Gasparetto, Marco; Ross, Alex; Lee, Claire; Mak, Tim N.; Koo, Bon–Kyoung; Kumar, Nitin; Lawley, Trevor D.; Sinha, Anupam; Rosenstiel, Philip; Heuschkel, Robert; Stegle, Oliver; Zilbauer, Matthias

doi:10.1053/j.gastro.2017.10.007

Cited by 247 publications

(240 citation statements)

References 41 publications

Supporting

Mentioning

216

Contrasting

Order By: Relevance

“…Microbiota-sensitive epigenetic signatures were recently observed for histone methylation in CD 48 . While the largest difference in methylation patterns was attributed to inflammation, as expected due to disproportionate composition of inflammatory cells 49 , we did observe significant epigenome-wide differences between CD and control groups (visualized by principal component 6 in Fig. 4).…”

Section: Discussionsupporting

confidence: 63%

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

et al. 2020

View full text Add to dashboard Cite

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.

show abstract

Section: Discussionsupporting

confidence: 63%

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In agreement with the largest study selected for our meta-analysis 9 , genes near abnormal DNA methylation were enriched in immune and inflammatory pathways, highlighting the role of chronic inflammation in both, UC and CD. In particular, TGF- is a cytokine able to modulate the inflammatory response, and it was enriched in IBD-DMRs.…”

Section: Discussionsupporting

confidence: 84%

“…While genetics explains a fraction of inheritance of IBD (13,1% variance in CD and 8,2% in UC) 7 , environmental factors are able to influence susceptibility through non-genetic mechanisms, such as DNA methylation 8 . Indeed, several recent studies have provided a detailed characterization of genomic abnormalities in IBD, including DNA methylation [9][10][11] . Mechanistically placed between the genome and the transcriptome, DNA methylation may represent an effector of genetic variants and the resulting pathological phenotype 8 .…”

Section: Introductionmentioning

confidence: 99%

The DNA Methylome of Inflammatory Bowel Disease (IBD) reflects intrinsic and extrinsic factors in intestinal epithelial cells

Agliata

Fernández-Jiménez

Goldsmith

et al. 2019

Preprint

View full text Add to dashboard Cite

Abnormal DNA methylation has been described in human inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD). As other complex diseases, IBD results from the balance between genetic predisposition and environmental exposures. As such, DNA methylation may be placed as an effector of both, genetic susceptibility variants and/or environmental signals such as cytokine exposure. We attempted to discern between these two non-excluding possibilities by performing a meta-analysis of DNA methylation data in intestinal

show abstract

“…Intestinal organoids are being used to study not only basic intestinal physiology [6], but also pathophysiological processes, for example, TNFα-induced epithelial cell death during inflammatory bowel disease [7,8]. Moreover, intestinal organoids have been used to study host–pathogen interactions, for example, during Zika virus infection [9].…”

mentioning

confidence: 99%

A Fast and Simple Fluorometric Method to Detect Cell Death in 3D Intestinal Organoids

et al. 2019

View full text Add to dashboard Cite

Organoids recapitulate the (patho)physiological processes in certain tissues and organs closer than classical cell lines. Therefore, organoid technology offers great potentials in drug development and testing, and personalized medicine. In particular, organoids can be used to study and predict drug-induced toxicity in certain tissues. However, until today few methods had been reported to analyze cell death in 3D-microtissues in a quantitative manner. Here, we describe a novel fluorometric method for the quantitative measurement of specific organoid cell death. Organoids are stained simultaneously with the cell impermeable nuclear dye propidium iodide and cell permeable Hoechst33342. While Hoechst allows in-well normalization to cell numbers, propidium iodide detects relative proportion of dead cells independent of hydrogel. Measurement and analysis time, as well as usability are drastically improved in comparison to other established methods. Parallel multiplexing of our method with established assays measuring mitochondrial activity further enhances its applicability in personalized medicine and drug discovery.

show abstract

DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome

Cited by 247 publications

References 41 publications

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease

The DNA Methylome of Inflammatory Bowel Disease (IBD) reflects intrinsic and extrinsic factors in intestinal epithelial cells

A Fast and Simple Fluorometric Method to Detect Cell Death in 3D Intestinal Organoids

Contact Info

Product

Resources

About