Happy thanksgiving!🍁

Thanks:)

Thank you, Neha!!

Thank you, Genevieve!!!☺️

9/9 We hope this model will deepen our understanding of the origins of human #EwingSarcoma and will speed the development of better therapies. @amatrudalab.bsky.social

8/9. Strikingly, EWSR1::FLI1-expressing cells induced ectopic fin formation by locally activating Fgfr and Hox signaling, eventually giving rise to tumors. This suggests that pre-tumor cells hijack developmental programs to establish a local signaling environment for tumor initiation.

7/9 By integrating chromatin accessibility with genome-wide EWSR1::FLI1 binding profiles, we show that the fusion reprograms cells by binding ETS motif-containing developmental enhancers. We also observed EWSR1::FLI1 binding to GGAA repeats, consistent with human data.

6/9 Single-cell transcriptomic and chromatin profiling of zebrafish tumors revealed that EWSR1::FLI1 expression in neural crest cells drives a mesenchymal/mesodermal shift, with mesodermal genes like #Brachyury (T) strongly upregulated. #NCCs #mesoderm #reprogramming

5/9. Next, we generated a stable zebrafish line with tissue-specific expression of human EWSR1::FLI1 in NCCs. This led to the development of pre-tumor outgrowths and, eventually, massive tumors, demonstrating that the expression of the oncofusion in NCCs is tumorigenic in vivo.

4/9 First, using our mosaic zebrafish model of Ewing sarcoma, we traced EWSR1::FLI1 positive cells in early development and found that lineage, timing, and expression level of the oncofusion are critical. In our model, neural crest cells uniquely tolerated this toxic oncofusion in vivo.

3/9 In this study, we use zebrafish genetic cancer models to investigate the origin of #EwingSarcoma. We show that EWSR1::FLI1 alters embryonic cell fate decisions, reprogramming neural crest cells into a mesoderm-like state that initiates this devastating childhood cancer.

2/9 Huge thanks to Dr. Arata @clairearataphd and Dr. Crump @crumplab.bsky.social, and the amazing @childrensLA environment that made this work possible. Very grateful to my mentor, Dr. Amatruda @amatrudalab.bsky.social, and our fantastic Lab.

Congratulations, John!!

Look forward to talking to you at the seminar!