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Series GSE213326 Query DataSets for GSE213326
Status Public on Jun 13, 2024
Title A chronic signaling TGFb zebrafish reporter identifies immune response in melanoma [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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.
 
Overall design ChIP-seq +/- TGFB1
ChIP-seq on A375s treated with 10ng/mL TGFB1 ligand or vehicle control
A375 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.
 
Contributor(s) Noonan HR, Barbano J, Xifaras M, Baron CS, Yang S, Koczirka K, McConnell A, Zon L
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Submission date Sep 14, 2022
Last update date Jun 14, 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
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (16)
GSM6578998 Vehicle Control A375 INPUT 6.11.18
GSM6578999 TGFB1 stimulated A375 INPUT 6.11.18
GSM6579000 Vehicle Control A375 H3K27ac 6.11.18
This SubSeries is part of SuperSeries:
GSE213360 A chronic signaling TGFb zebrafish reporter identifies immune response in melanoma
Relations
BioProject PRJNA880538

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE213326_RAW.tar 9.2 Mb (http)(custom) TAR (of NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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