|
| Status |
Public on Nov 08, 2012 |
| Title |
Gene expression profiles of Notch signaling suppression in prostate basal cells. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The role of Notch signaling in the maintenance and differentiation of adult prostate stem cells remains unclear. We found that Notch ligands are mainly expressed within the basal cell lineage, while active Notch signaling is detected in both the prostate basal and luminal cell lineages. Disrupting the canonical Notch effector RBP-J impairs the differentiation of prostate basal stem cells and increases their proliferation in vitro and in vivo, but does not affect luminal cell biology. Conversely, ectopic Notch activation in adult prostates results in basal cell depletion and luminal cell hyper-proliferation. TGFβ dominates over Notch and overrides Notch ablation-induced proliferation of prostate basal cells. In turn, Notch confers positive feedback by up-regulating a plethora of TGFβ signaling components including TGFβRI. These findings reveal crucial roles of the self-enforced positive reciprocal regulatory loop between TGFβ and Notch in maintaining prostate basal stem cell dormancy.
|
| |
|
| Overall design |
We employed an in vitro prostate sphere assay to further investigate how Notch signaling regulates basal cell proliferation and differentiation. FACS isolated adult murine prostate basal cells (using FVB mice) were cultured in the prostate sphere assay with or without N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester (DAPT), an inhibitor for the γ-Secretase complex. Gene expression profiles were taken of vehicle- and DAPT-treated prostate spheres.
|
| |
|
| Contributor(s) |
Creighton C, Xin L, Valdez J |
| Citation(s) |
23122291 |
| Submission date |
Dec 01, 2011 |
| Last update date |
May 10, 2018 |
| Contact name |
Chad Creighton |
| E-mail(s) |
creighto@bcm.tmc.edu
|
| Organization name |
Baylor College of Medicine
|
| Department |
Biostatistics, Ducan Cancer Center
|
| Street address |
One Baylor Plaza, Mail Stop: BCM305
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
|
| Samples (4)
|
| GSM841217 |
FACS isolated adult murine prostate basal cells, cultured in vitro and vehicle-treated 1 |
| GSM841218 |
FACS isolated adult murine prostate basal cells, cultured in vitro and vehicle-treated 2 |
| GSM841219 |
FACS isolated adult murine prostate basal cells, cultured in vitro and DAPT-treated 1 |
| GSM841220 |
FACS isolated adult murine prostate basal cells, cultured in vitro and DAPT-treated 2 |
|
| Relations |
| BioProject |
PRJNA150011 |
Less...
More...