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| Status |
Public on Dec 31, 2014 |
| Title |
Ascl2 acts as an R-spondin/Wnt responsive switch to control stemness in intestinal crypts [array] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Wnt signals control three functions of intestinal crypts: maintenance of Lgr5 stem cells, proliferation of transit-amplifying daughters and formation of Paneth cells. Here, we study how the Wnt effector β-catenin/Tcf4 cooperates with the Wnt-activated transcription factor Ascl2 to control a stem cell transcription program. DNA elements that are co-occupied and synergistically regulated by Ascl2 and Tcf4 specifically map to stem cell genes. In vitro, Tcf4-/- mini-guts are rescued by Ascl2 expression, while Ascl2-/- organoids are rescued by Wnt signaling. A direct auto-activatory loop leads to an on/off expression pattern of Ascl2 with a threshold that depends on the previous state. Wnt/R-spondin1 activates this loop. This mechanism interprets Wnt levels in crypts and translates this continuous signal into a discrete Ascl2 “on” or “off” decision. In turn Ascl2, together with β-catenin/Tcf, activates stem cell genes. Thus, Ascl2 forms a transcriptional 'stemness switch' that is both Wnt-responsive and Wnt-dependent.
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| Overall design |
Expression was profiled from organoids from different genetic backgrounds and under different treatements
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| Contributor(s) |
Schuijers J, Clevers H |
| Citation(s) |
25620640 |
| Submission date |
Apr 24, 2014 |
| Last update date |
May 10, 2018 |
| Contact name |
Jurian Schuijers |
| Organization name |
Hubrecht Insitute
|
| Street address |
Uppsalalaan 8
|
| City |
Utrecht |
| State/province |
Utrecht |
| ZIP/Postal code |
3584CT |
| Country |
Netherlands |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE84457 |
Ascl2 acts as an R-spondin/Wnt responsive switch to control stemness in intestinal crypts |
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| Relations |
| BioProject |
PRJNA245327 |
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