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| Status |
Public on Feb 04, 2020 |
| Title |
IκBα deficiency imposes a fetal phenotype to intestinal stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The intestinal epithelium is a paradigm of adult tissue in constant regeneration that is supported by intestinal stem cells (ISCs). The mechanisms regulating ISC homeostasis after injury are poorly understood. We previously demonstrated that IκBa, not only controls NF-κB activation, but also exerts nuclear functions as cytokine sensor in a subset of PRC2-regulated genes. We now uncover nuclear phosphorylated IκBa (P-IκBa) in the ISC compartment where it binds highly histone methylated genomic regions. Mice deficient for IκBa show aberrant distribution of H3K27me3 mark, and altered intestinal differentiation with persistence of a fetal-like ISC signature. In vitro, IκBa deficient intestinal cells produced morphologically aberrant organoids carrying a PRC2, Notch and IFN-dependent fetal-like transcriptional signature. Induction of the fetal-like phenotype by DSS treatment is associated with loss of nuclear P-IκBa in the damaged colonic epithelium and it subsequent accumulation in early CD44 positive regenerating areas. Importantly, IκBa deficient animals showed higher resistance to damage, likely due to persistent fetal-like phenotype. These results point out intestinal IκBa as chromatin sensor of inflammation in the ISC compartment.
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| |
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| Overall design |
10 samples were analyzed: WT (n=5); KO (n=5);
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| |
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| Contributor(s) |
Blay LE, Aylagas LM |
| Citation(s) |
32270911 |
| Submission date |
May 08, 2019 |
| Last update date |
Oct 19, 2023 |
| Contact name |
Júlia Perera-Bel |
| E-mail(s) |
mardata-bu@researchmar.net
|
| Organization name |
Hospital del Mar Research Institute
|
| Department |
MARData-BU
|
| Street address |
Doctor Aiguader, 88
|
| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
|
| Samples (10)
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| Relations |
| BioProject |
PRJNA541989 |
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