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GEO help: Mouse over screen elements for information. |
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Status |
Public on Sep 21, 2022 |
Title |
DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon [RNA-seq] |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Genetic variants in the DNMT3A locus have been associated with inflammatory bowel disease (IBD). DNMT3A is part of the epigenetic machinery physiologically involved in DNA methylation. We show that DNMT3A plays a critical role in maintaining intestinal homeostasis and gut barrier function. DNMT3A expression is downregulated in intestinal epithelial cells (IECs) from IBD patients and upon TNF treatment in murine intestinal organoids. Ablation of DNMT3A in Caco-2 cells results in global DNA hypomethylation, which is linked to impaired regenerative capacity, transepithelial resistance and intercellular junction formation. Genetic deletion of Dnmt3a in IECs (Dnmt3aΔIEC) in mice confirms the phenotype of an altered epithelial ultrastructure with shortened apical-junctional complexes, reduced Goblet cell numbers and increased intestinal permeability in the colon in vivo. Dnmt3aΔIEC mice suffer from increased susceptibility to experimental colitis, characterized by reduced epithelial regeneration. These data demonstrate a critical role for DNMT3A in orchestrating intestinal epithelial homeostasis and response to tissue damage and suggest an involvement of impaired epithelial DNMT3A function in the etiology of IBD.
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Overall design |
For the in vitro experiment with Caco-2 cells, 4 groups have been analyzed with 4 replicates each. For in vivo experiment using purified intestinal epithelial cells from Dnmt3a △IEC in steady state, 4 wild type mice and 4 Dnmt3a △IEC mice were used.
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Contributor(s) |
Mishra N, Fazio A, Bordoni D, Rosenstiel P |
Citation(s) |
36271073 |
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Submission date |
Aug 08, 2022 |
Last update date |
Nov 02, 2022 |
Contact name |
Neha Mishra |
E-mail(s) |
n.mishra@ikmb.uni-kiel.de
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Organization name |
Institute of Clinical Molecular Biology
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Lab |
Cell biology Lab
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Street address |
Rosalind-Franklin-Str. 12
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City |
Kiel |
ZIP/Postal code |
24105 |
Country |
Germany |
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Platforms (2) |
GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (24)
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GSM6435808 |
Caco2_3A2-1, RNA |
GSM6435809 |
Caco2_WT-2, RNA |
GSM6435810 |
Caco2_3AKO-2, RNA |
GSM6435811 |
Caco2_3A1-2, RNA |
GSM6435812 |
Caco2_3A2-2, RNA |
GSM6435813 |
Caco2_WT-3, RNA |
GSM6435814 |
Caco2_3AKO-3, RNA |
GSM6435815 |
Caco2_3A1-3, RNA |
GSM6435816 |
Caco2_3A2-3, RNA |
GSM6435817 |
Caco2_WT-4, RNA |
GSM6435818 |
Caco2_3AKO-4, RNA |
GSM6435819 |
Caco2_3A1-4, RNA |
GSM6435820 |
Caco2_3A2-4, RNA |
GSM6435821 |
Dnmt3aVillin717, RNA |
GSM6435822 |
Dnmt3aVillin718, RNA |
GSM6435823 |
Dnmt3aVillin719, RNA |
GSM6435824 |
Dnmt3aVillin720, RNA |
GSM6435825 |
Dnmt3aVillin721, RNA |
GSM6435826 |
Dnmt3aVillin722, RNA |
GSM6435827 |
Dnmt3aVillin723, RNA |
GSM6435828 |
Dnmt3aVillin724, RNA |
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This SubSeries is part of SuperSeries: |
GSE210763 |
DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon |
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Relations |
BioProject |
PRJNA867198 |
Supplementary file |
Size |
Download |
File type/resource |
GSE210714_RAW.tar |
94.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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