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| Status |
Public on Mar 06, 2023 |
| Title |
SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance.. [scRNAseq] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Renal medullary carcinoma (RMC) is an aggressive tumour driven by bi-allelic loss of SMARCB1 and tightly associated with sickle cell trait. However, the cell-of-origin and oncogenic mechanism remain poorly understood. Using single-cell sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into an epithelial-mesenchymal gradient of RMC cells associated with loss of renal epithelial transcription factors TFCP2L1, HOXB9 and MITF and gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs. We describe the molecular basis for this transcriptional switch that is reversed by SMARCB1 re-expression repressing the oncogenic and ferroptosis resistance programs leading to ferroptotic cell death. Ferroptosis resistance links TAL cell survival with the high extracellular medullar iron concentrations associated with sickle cell trait, an environment propitious to the mutagenic events associated with RMC development. This unique environment may explain why RMC is the only SMARCB1-deficient tumour arising from epithelial cells, differentiating RMC from rhabdoid tumours arising from neural crest cells.
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| Overall design |
ScRNA-seq of naive RMC tumor, treated RMC tumor with its native adjacent tissue, and patient-derived xenograft RMC tumor.
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| Contributor(s) |
Helleux A, Davidson G, Vokshi B, Bouarich R, Manriquez V, Jean De Dieu Andrianteranagna M, Davidson I, Malouf G, Bourdeaut F |
| Citation(s) |
37236926 |
| |
| Submission date |
Jul 28, 2021 |
| Last update date |
Jun 05, 2023 |
| Contact name |
Guillaume Davidson |
| E-mail(s) |
davidsoy@igbmc.fr
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| Organization name |
IGBMC
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| Street address |
1 Rue Laurent Fries
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| City |
Strasbourg |
| ZIP/Postal code |
67404 |
| Country |
France |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL25431 |
Illumina HiSeq 4000 (Homo sapiens; Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE181001 |
SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance. |
|
| Relations |
| BioProject |
PRJNA750394 |
| SRA |
SRP330210 |
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