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| Status |
Public on Apr 21, 2020 |
| Title |
Discrete regulation of β-catenin-mediated transcription governs identity of intestinal epithelial stem cells [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The homeostasis of the gut epithelium relies upon continuous renewal and proliferation of crypt-resident intestinal epithelial stem cells (IESCs). Wnt/β-catenin signaling is required for IESC maintenance, however, it remains unclear how this pathway selectively governs the identity and proliferative decisions of IESCs. Here, we demonstrate that C-terminally-recruited transcriptional co-factors of β-catenin act as all-or-nothing regulators of Wnt-target gene expression. Blocking their interactions with β-catenin rapidly induces loss of IESCs and intestinal homeostasis. Conversely, N-terminally recruited co-factors fine-tune β-catenin’s transcriptional output to ensure proper self-renewal and proliferative behaviour of IESCs. Impairment of N-terminal interactions triggers transient hyperproliferation of IESCs, resulting in exhaustion of the self-renewing stem cell pool. IESC mis-differentiation, accompanied by intrinsic and extrinsic stress signalling results in a process resembling aberrant "villisation" of intestinal crypts. Our data suggest that IESC-specific Wnt/β-catenin output requires discrete regulation of transcription by transcriptional co-factors.
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| |
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| Overall design |
RNA sequencing of bulk extracts of murine small intestinal epithelium of betacatenin-mutant mice (4xcontrol, 3xD164A, 2xDeltaC, 2xdm, 2xKO)
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| |
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| Contributor(s) |
Borrelli C, Valenta T |
| Citation(s) |
33649334 |
| |
| Submission date |
Apr 20, 2020 |
| Last update date |
Mar 16, 2021 |
| Contact name |
Tomas Valenta |
| E-mail(s) |
tomas.valenta@mls.uzh.ch
|
| Organization name |
University of Zurich
|
| Department |
Institute of Molecular Life Sciences
|
| Street address |
Winterthurerstrasse 190
|
| City |
Zurich |
| ZIP/Postal code |
CH-8057 Zurich |
| Country |
Switzerland |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (13)
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| This SubSeries is part of SuperSeries: |
| GSE148943 |
Discrete regulation of β-catenin-mediated transcription governs identity of intestinal epithelial stem cells |
|
| Relations |
| BioProject |
PRJNA626595 |
| SRA |
SRP257515 |
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