ArticlePloS one2015
Overlapping DNA methylation dynamics in mouse intestinal cell differentiation and early stages of malignant progression.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Cell fate specification and differentiation in the adult mammalian intestine.Nature reviews. Molecular cell biology · 2021Review
- UVB induces cutaneous squamous cell carcinoma progression by de novo ID4 methylation via methylation regulating enzymes.EBioMedicine · 2020Article
- Intestinal Epithelial Organoids as Tools to Study Epigenetics in Gut Health and Disease.Stem cells international · 2019Review
- Article
- Inactivation of Adenomatous Polyposis Coli Reduces Bile Acid/Farnesoid X Receptor Expression through Fxr gene CpG Methylation in Mouse Colon Tumors and Human Colon Cancer Cells.The Journal of nutrition · 2016Article
- DNA Methylation Dynamics During Differentiation, Proliferation, and Tumorigenesis in the Intestinal Tract.Stem cells and development · 2015Review
- Epigenetic alterations in gastric cancer (Review).Molecular medicine reports · 2015Review
- Epigenetic Inheritance From Normal Origin Cells Can Determine the Aggressive Biology of Tumor-Initiating Cells and Tumor Heterogeneity.Cancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mouse models of intestinal crypt cell differentiation and tumorigenesis have been used to characterize the molecular mechanisms underlying both processes. DNA methylation is a key epigenetic mark and plays an important role in cell identity and differentiation programs and cancer. To get insights into the dynamics of cell differentiation and malignant transformation we have compared the DNA methylation profiles along the mouse small intestine crypt and early stages of tumorigenesis. Genome-scale analysis of DNA methylation together with microarray gene expression have been applied to compare intestinal crypt stem cells (EphB2high), differentiated cells (EphB2negative), ApcMin/+ adenomas and the corresponding non-tumor adjacent tissue, together with small and large intestine samples and the colon cancer cell line CT26. Compared with late stages, small intestine crypt differentiation and early stages of tumorigenesis display few and relatively small changes in DNA methylation. Hypermethylated loci are largely shared by the two processes and affect the proximities of promoter and enhancer regions, with enrichment in genes associated with the intestinal stem cell signature and the PRC2 complex. The hypermethylation is progressive, with minute levels in differentiated cells, as compared with intestinal stem cells, and reaching full methylation in advanced stages. Hypomethylation shows different signatures in differentiation and cancer and is already present in the non-tumor tissue adjacent to the adenomas in ApcMin/+ mice, but at lower levels than advanced cancers. This study provides a reference framework to decipher the mechanisms driving mouse intestinal tumorigenesis and also the human counterpart.
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