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| Status |
Public on Jun 13, 2024 |
| Title |
A chronic signaling TGFb zebrafish reporter identifies immune response in melanoma [RNA-seq, ZMEL] |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Developmental signaling pathways associated with growth factors such as TGFb are commonly dysregulated in melanoma. Here we identified a human TGFb enhancer that was specifically activated in melanoma cells treated with TGFB1 ligand. We generated stable transgenic zebrafish with this enhancer driving green fluorescent protein (TIE:EGFP). EGFP was not expressed in normal melanocytes or early melanomas but was expressed in spatially distinct regions of mature melanomas. Single cell RNA-sequencing revealed that TIE:EGFP+ melanoma cells down-regulated interferon response, while up-regulating a novel set of chronic TGFb target genes. AP-1 factor binding is required for activation of this chronic TGFb reporter. Overexpression of the chromatin remodeler, SATB2, which is associated with tumor spreading shows activation of TGFb signaling in melanoma precursor zones and early melanomas. Confocal imaging and flow cytometric analysis showed that macrophages are recruited to EGFP positive regions and preferentially phagocytose TIE:EGFP+ cells. This work identifies a TGFb induced immune response and demonstrates the need for the development of chronic TGFb biomarkers to predict patient response to TGFb inhibitors.
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| Overall design |
RNA-seq +/- TGFB1
Bulk RNA-seq on ZMEL1 treated with 10ng/mL TGFB1 ligand or vehicle control
ZMEL1 cells were serum starved for 2 hours, then treated with 10ng/mL human recombinant TGFB1 or 4mM HCl containing 1 mg/mL BSA vehicle control for an additional two hours. Experiment performed in technical triplicate.
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| Contributor(s) |
Noonan HR, Barbano J, Xifaras M, Baron CS, Yang S, Koczirka K, McConnell A, Zon L |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 14, 2022 |
| Last update date |
Jun 13, 2024 |
| Contact name |
Leonard Zon |
| E-mail(s) |
zon@enders.tch.harvard.edu
|
| Organization name |
Boston Children's Hospital
|
| Department |
Oncology/Hematology
|
| Street address |
1 Blackfan Circle
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL21741 |
Illumina HiSeq 4000 (Danio rerio) |
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| Samples (6)
|
| GSM6579020 |
Vehicle Control treated ZMEL1 Replicate 1 |
| GSM6579021 |
Vehicle Control treated ZMEL1 Replicate 2 |
| GSM6579022 |
Vehicle Control treated ZMEL1 Replicate 3 |
| GSM6579023 |
10ng/mL TGFB1 treated ZMEL1 Replicate 1 |
| GSM6579024 |
10ng/mL TGFB1 treated ZMEL1 Replicate 2 |
| GSM6579025 |
10ng/mL TGFB1 treated ZMEL1 Replicate 3 |
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| This SubSeries is part of SuperSeries: |
| GSE213360 |
A chronic signaling TGFb zebrafish reporter identifies immune response in melanoma |
|
| Relations |
| BioProject |
PRJNA880540 |
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