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| Status |
Public on Sep 30, 2023 |
| Title |
PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma. FP-RMS histologically resembles developing muscle yet occurs throughout the body in areas devoid of skeletal muscle highlighting that FP-RMS is not derived from an exclusively myogenic cell of origin. Here we demonstrate that P3F reprograms mouse and human endothelial progenitors to FP-RMS. We show that P3F expression in aP2-Cre expressing cells reprograms endothelial progenitors to functional myogenic stem cells capable of regenerating injured muscle fibers. Further, we describe a FP-RMS mouse model driven by P3F expression and Cdkn2a loss in endothelial cells. Additionally, we show that P3F expression in TP53-null human iPSCs blocks endothelial-directed differentiation and guides cells to become myogenic cells that form FP-RMS tumors in immunocompromised mice. Together these findings demonstrate that FP-RMS can originate from aberrant development of non-myogenic cells driven by P3F.
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| Overall design |
RNA was harvested at Day 0 and Day 15 of a 14 day Endothelial differentiation protcol. Cells were transduced with P3F or left untreated at Day 5 of the protocol so that we could deteremine the effect of enforced P3F expression on endothelial differentiation
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| Contributor(s) |
Searcy MB, Jin H, Gadek K, Stevens B, Larsen R, Hatley ME |
| Citation(s) |
37968277 |
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| Submission date |
Aug 24, 2023 |
| Last update date |
Jan 03, 2024 |
| Contact name |
Hongjian Jin |
| E-mail(s) |
hongjian.jin@STJUDE.ORG
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| Organization name |
St Jude Children's Research Hospital
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| Department |
Center for Applied Bioinformatics
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| Street address |
262 Danny Thomas Place
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38015 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE218274 |
PAX3-FOXO1 expression in endothelial progenitors dictates myogenic reprogramming and rhabdomyosarcoma identity |
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| Relations |
| BioProject |
PRJNA1009038 |
