|
| Status |
Public on Feb 04, 2020 |
| Title |
IκBα deficiency imposes a fetal phenotype to intestinal stem cells [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| 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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| Overall design |
16 samples analyzed, plus two different inputs
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| |
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| Contributor(s) |
Espinosa Blay L, Marruecos Aylagas L |
| Citation(s) |
32270911 |
| |
| Submission date |
May 14, 2019 |
| Last update date |
May 05, 2020 |
| Contact name |
Lluis Espinosa |
| E-mail(s) |
lespinosa@imim.es
|
| Phone |
+34-933160589
|
| Organization name |
Hospital del Mar
|
| Department |
Institut Municipal d'Investigacions Mèdiques, (IMIM)
|
| Lab |
Stem Cell and Cancer
|
| Street address |
Dr. Aiguader 88
|
| City |
Barcelona |
| State/province |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (18)
|
| GSM3765449 |
p65 ChIP-seq from P6 WT intestinal cells [W1P6] |
| GSM3765450 |
p65 ChIP-seq from P6 WT intestinal cells [W2P6] |
| GSM3765451 |
p65 ChIP-seq from P6 IkBa KO intestinal cells [K8P6] |
| GSM3765452 |
p65 ChIP-seq from P6 IkBa KO intestinal cells [K9P6] |
| GSM3765453 |
SUZ12 ChIP-seq from P6 WT intestinal cells [W1SZ] |
| GSM3765454 |
SUZ12 ChIP-seq from P6 WT intestinal cells [W2SZ] |
| GSM3765455 |
SUZ12 ChIP-seq from P6 IkBa KO intestinal cells [K8SZ] |
| GSM3765456 |
SUZ12 ChIP-seq from P6 IkBa KO intestinal cells [K9SZ] |
| GSM3765457 |
IkBa ChIP-seq from P6 WT intestinal cells [W4CI] |
| GSM3765458 |
IkBa ChIP-seq from P6 WT intestinal cells [W4DI] |
| GSM3765459 |
IkBa ChIP-seq from P6 WT intestinal cells [W5CI] |
| GSM3765460 |
IkBa ChIP-seq from P6 WT intestinal cells [W5DI] |
| GSM3765461 |
H3K27me3 ChIP-seq from P6 WT intestinal cells [W1H3] |
| GSM3765462 |
H3K27me3 ChIP-seq from P6 WT intestinal cells [W2H3] |
| GSM3765463 |
H3K27me3 ChIP-seq from P6 IkBa KO intestinal cells [K8H3] |
| GSM3765464 |
H3K27me3 ChIP-seq from P6 IkBa KO intestinal cells [K9H3] |
| GSM3765465 |
Input from P6 IkBa KO intestinal cells [INKO] |
| GSM3765466 |
Input from P6 WT intestinal cells [INWT] |
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| This SubSeries is part of SuperSeries: |
| GSE131187 |
IκBα deficiency imposes a fetal phenotype to intestinal stem cells |
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| Relations |
| BioProject |
PRJNA542867 |
| SRA |
SRP198383 |
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