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Series GSE32425 Query DataSets for GSE32425
Status Public on Dec 01, 2012
Title Expression profile of zebrafish embryonal rhabdomyosarcoma
Organism Danio rerio
Experiment type Expression profiling by array
Summary Fluorescent-labeled zebrafish RAS-induced embryonal rhabdomyosarcoma (ERMS) were created to facilitate in vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in diverse cellular compartments. Using this strategy, we have identified a molecularly distinct ERMS cell subpopulation that expresses high levels of myf5 and is enriched for ERMS-propagating potential when compared with other tumor-derived cells.
Embryonal rhabdomyosarcoma (ERMS) is an aggressive pediatric sarcoma of muscle. Here, we show that tumor-propagating potential is confined to myf5+ERMS cells and can be visualized in live, fluorescent transgenic zebrafish. During early tumor growth, myf5+ERMS cells reside within an expanded satellite cell compartment, but by late stage ERMS, myf5+cells are dynamically reorganized into distinct regions separated from differentiated tumor cells. Human ERMS also contain distinct areas of differentiated and undifferentiated cells. Time-lapse imaging revealed that myf5+ERMS cells populate newly formed tumor only after seeding by highly migratory myogenin+ ERMS cells. This finding helps explain the clinical observation that Myogenin positivity correlates with poor clinical outcome in human ERMS and suggests that differentiated tumor cells play critical roles in metastasis.
Overall design One-cell stage myf5-GFP/mylz2-mCherry fluorescent transgenic zebrafish were injected with rag2-kRAS12D. A subset of animals developed ERMS. Tumor cells were transplanted into syngeneic recipient animals that lacked fluorescent reporter expression. ERMS cell subfractions were isolated from transplant animals and purified cell populations obtained following two rounds of FACS. Sorted cells were 1) analyzed by microarray/RT-PCR and 2) transplanted at limiting dilution into syngeneic animals. These experiments confirm that zebrafish ERMS contain molecularly distinct cell subfractions that express high levels of myf5-GFP and exhibit difference in gene expression when compared to other ERMS cell subtypes. All four fluorescent-labeled cell populations were analyzed (n=2 tumors total).
Contributor(s) Langenau DM, Ignatius MS
Citation(s) 22624717
Submission date Sep 27, 2011
Last update date Jan 25, 2018
Contact name David M Langenau
Phone 617643-6508
Organization name Massachusetts General Hospital
Department Molecular Pathology
Lab Langenau Lab
Street address 149 13th Street #6012
City Charlestown
State/province MA
ZIP/Postal code 02180
Country USA
Platforms (1)
GPL1319 [Zebrafish] Affymetrix Zebrafish Genome Array
Samples (8)
GSM802469 Tumor #1, GFP+/mCherry-negative sorted cells
GSM802470 Tumor #1, GFP+/mCherry+, Double Positive (DP) sorted cells
GSM802471 Tumor #1, GFP-negative/mCherry+ sorted cells
BioProject PRJNA147915

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Supplementary file Size Download File type/resource
GSE32425_RAW.tar 13.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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