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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 25, 2021 |
| Title |
Cell-to-cell variability in PAX3:FOXO1 expression determines tumorigenic potential in rhabdomyosarcoma |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The rhabdomyosarcoma (RMS) cell pool is phenotypically and functionally heterogeneous. Low passage cell lines established from Myf6Cre,Pax3:Fkhr,p53 mouse RMS and primary human RMS cultures were used to demonstrate marked heterogeneity in PAX3:FOXO1 (P3F) expression at the single-cell level. In mouse Myf6Cre,Pax3:Fkhr,p53 RMS cells, expression of P3F is directed by the Pax3 promoter and coupled to an eYFP fluorescent marker. YFPlow/ P3Flow mouse RMS cells included 87±0.2% G0/ G1 cells, differentially expressed transcripts involved in extracellular matrix interaction and reorganized their actin cytoskeleton to produce a cellular phenotype characterized by more efficient adhesion and migration compared to YFPhigh/ P3Fhigh cells. By contrast, 49±3.2% of YFPhigh/ P3Fhigh cells were in the G2/ M phase of the cell cycle, and higher P3F expression correlated with higher proliferation rates. These differences translated into higher tumor-propagating cell frequencies in limiting dilution analyses and higher clonal activity of YFPlow/ P3Flow compared to YFPhigh/ P3Fhigh cells. Both YFPlow/ P3Flow and YFPhigh/P3Fhigh cells gave rise to mixed clones, consistent with fluctuations in P3F expression at the cellular level over time. Finally, exposure to the anti-tropomyosin compound TR100 disrupted the actin cytoskeleton and reversed more efficient migration and adhesion in YFPlow/ P3Flow RMS cells. We speculate that conversion from one phenotype to another may result in adaptive plasticity and may provide a critical advantage during tumor progression
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| Overall design |
We performed ATAC-Seq on YFP high / P3F high and YFP low / P3F low cells isolated from mouse rhabdomyosarcoma cells U23674.
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| Contributor(s) |
Ku M, Ke E, Regina C, Hettmer S |
| Citation(s) |
34187933 |
| Submission date |
Jul 15, 2020 |
| Last update date |
Jul 06, 2021 |
| Contact name |
Manching Ku |
| Organization name |
Medical Center - University of Freiburg
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| Department |
Hematology and Oncology
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| Street address |
Mathildenstrasse 1
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| City |
Freiburg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA646365 |
| SRA |
SRP271996 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE154452_RAW.tar |
380.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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