GSE191132
Single-cell gene expression profiles associated with myxoid liposarcoma scaffold culture compared to xenograft and effect of fusion oncogene FUS-DDIT3
Myxoid liposarcoma (MLS) is the second most common type of liposarcoma and is characterized by the fusion oncogene FUS-DDIT3 or the less common EWSR1-DDIT3. While the presence of FUS-DDIT3 as a driver oncoprotein in most MLS cases has been confirmed, the exact molecular action behind the capacity of FUS-DDIT3 for transformation is still unclear and therefore creates a challenge in finding new treatments against this type of cancer. The importance of the microenvironment for tumor progression have long been accepted and might also influence the effect of the fusion oncoprotein. However, due to a lack of relevant experimental model systems, it has been challenging to examine the microenvironmental impact in myxoid liposarcoma development. Therefore, we have developed a new model system utilizing scaffolds derived from myxoid liposarcoma patient-derived xenograft tumors that are decellularized and then repopulated with sarcoma cell lines. This cell culture system mimics in vivo-like tumor cell growth conditions and induce transcriptional changes within the cells. In order to investigate the effect of the microenvironment as well as the fusion oncogene, we analyzed myxoid liposarcoma cell lines as well as fibrosarcoma cells with and without ectopic FUS-DDIT3 expression cultured in scaffolds and adherent two-dimensional growth conditions. We identified several gene networks and processes that are uniquely associated with FUS-DDIT3 expression and with the microenvironment, respectively. The development of patient-derived scaffolds opens up new possibilities to understand tumor development. Overall design: Single cell RNA sequencing using 10x Genomics 3' solution of HT1080 fibrosarcoma cells with and without the fusion oncogene FUS-DDIT3.