Single-cell analysis of Myxoid liposarcoma reveals novel subpopulations and dysfunctional cell cycle regulation

Abstract
Sarcomas characterized by FET (FUS, EWSR1, TAF15) fusion oncogenes (FET sarcomas) contain a hierarchy of different cell types, forming subpopulations of cancer stem cells, proliferating expansion phase cells and differentiated cells. The most common entities of FET sarcomas are Myxoid liposarcoma are Ewing sarcoma. The identity and function of these subpopulations, and the pathways that control transitions between different cell states are essentially unknown in FET sarcomas. To facilitate studies of tumor subpopulations and their dynamic transitions into different cell states we are applying a qPCR based technique to simultaneously interrogate multiple analytes (DNA, mRNA, miRNA, ncRNA and proteins) in the same single-cell. This approach open up new avenues for detailed correlation studies of multiple and different classes of analytes at the single-cell level. Varimax and trend-PCA are new data visualization tools that simplify data interpretations facilitating discoveries. Here, we applied single-cell analysis to show that Myxoid liposarcoma has a dysfunctional cell cycle regulation. In addition, we identified a novel quiescent cell population with distinct expression profile. Importantly, the FET fusion oncogene can be linked to both these tumor characteristics. In this presentation we will also discuss how single-cell based analysis in general may help us to gain new and detailed information about cell states and cell fate decisions.