|
| Status |
Public on Jan 13, 2016 |
| Title |
Satb1 Overexpression Drives Tumor-Promoting Activities In Cancer-Associated Dendritic Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Special AT-rich sequence-binding protein-1 (Satb1) governs genome-wide transcriptional programs. Using a new conditional knockout mouse, we found that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating MHC-II expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC-II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46+ inflammatory DCs that universally infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. Correspondingly, specific in vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but relentless Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression.
|
| |
|
| Overall design |
RNA-seq with whild type and knocked-down Satb1
|
| |
|
| Contributor(s) |
Conejo-Garcia JR, Tesone AJ |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jan 12, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Priyankara J Wickramasinghe |
| E-mail(s) |
priyaw@wistar.org
|
| Phone |
2154956837
|
| Organization name |
The Wistar Institute
|
| Department |
Bioinformatics
|
| Lab |
Genomics
|
| Street address |
3601 Spruce Street
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (6)
|
| GSM2037720 |
control for experiment with highly downregulated Satb1, replicate 1 |
| GSM2037721 |
control for experiment with highly downregulated Satb1, replicate 2 |
| GSM2037722 |
highly downregulated Satb1, replicate 1 |
| GSM2037723 |
highly downregulated Satb1, replicate 2 |
| GSM2037724 |
control for experiment with low downregulation of Satb1, replicate 1 |
| GSM2037725 |
low downregulation of Satb1, replicate 1 |
|
| Relations |
| BioProject |
PRJNA308573 |
| SRA |
SRP068358 |
Less...
More...