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| Status |
Public on Sep 19, 2021 |
| Title |
Modeling Notch-induced tumor cell survival in the Drosophila ovary identifies cellular and transcriptional response to nuclear NICD accumulation |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Notch is a conserved developmental signaling pathway that is dysregulated in many cancer types, most often through constitutive activation. Tumor cells with nuclear accumulation of the active Notch receptor, NICD, generally exhibit enhanced survival while patients experience poorer outcomes. To understand the impact of NICD accumulation during tumorigenesis, we developed a tumor model using the Drosophila ovarian follicular epithelium. Using this system we demonstrated that NICD accumulation contributed to larger tumor growth, reduced apoptosis, increased nuclear size, and fewer incidents of DNA damage without altering ploidy. Using bulk RNA sequencing we identified the key Notch-induced targets involved in cell survival and DNA damage repair which were alternatively regulated prior to tumor formation. Finally, using single-cell RNA sequencing we demonstrated that genes contributing to many pathways are altered following tumor formation in a cell-type-specific manner. Ectopically expressing NICD produced dysregulated expression of genes involved in cell death regulation, immune and stress response, JAK/STAT signaling, cytoskeletal binding, adhesion, polarity, and growth regulation. This valuable tumor model for nuclear NICD accumulation in adult Drosophila follicle cells has allowed us to better understand the specific role of nuclear NICD accumulation in tumor cells in tumor cell survival and tumor progression.
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| Overall design |
Whole-tissue RNA-Seq (2 replicates per genotype; 2 time-points - 24h and 96h) of tjTS>GFP (Control) and tjTS>lglRNAi, tjTS>NICD and tjTS>NICD+lglRNAi (Samples) and single-cell RNA-Seq (1 replicate; 1 time-point - 72h) of w1118 cells (Control) of the Drosophila ovary and tjTS>lglRNAi, tjTS>NICD and tjTS>NICD+lglRNAi cells (Samples) of the Drosophila ovary. Single-cell RNA-Seq: 10x Genomics CHROMIUM Single Cell 3’ Solution V2 Chemistry and Sequencing platform: Illumina NovaSeq 6000.
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| Contributor(s) |
Chatterjee D |
| Citation(s) |
34571871 |
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| Submission date |
Aug 20, 2021 |
| Last update date |
Jan 12, 2022 |
| Contact name |
Wu-Min Deng |
| E-mail(s) |
wdeng7@tulane.edu
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| Organization name |
Tulane University
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| Department |
School of Medicine, Department of Biochemistry
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| Street address |
1700 Tulane Avenue
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| City |
New Orleans |
| State/province |
LA |
| ZIP/Postal code |
70112 |
| Country |
USA |
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| Platforms (1) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA756536 |
| SRA |
SRP333463 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE182505_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of CSV, MTX, ROBJ, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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