Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [RNA-seq]

Ewing sarcoma family of tumors (ESFT) is a uniquely human, highly aggressive bone and soft tissue malignancy peaking during adolescence characterized by EWSR1/ETS rearrangements. EWSR1/FLI1 expression is only tolerated in embryonic and mesenchymal stem cells (hESC and hMSC, respectively) that, although acquire ESFT transcriptional signatures, are devoid of tumorigenic potential. Here we report that ectopic EWSR1/FLI1 expression in hESC allows in vivo differentiation towards the three germ layers. In vitro, teratoma-derived hMSCs are devoid of transformation abilities. In vivo, these hMSCs led to the generation of T-cell lymphomas and ESFT-like tumors, composed of small-round blue cells. This new experimental approach constitutes a testing bench for the biology of translocation-dependent developmental tumors, from acute lymphoblastic leukemia to a variety of sarcomas. mRNA profiles of tumors derived from human Mesenchymal Stem Like Cells: two lymphomas from control hMSLCs, two lymphomas from EF_hMSLCs and two sarcomas from EF_hMSLCs