Single-cell profiling of alveolar rhabdomyosarcoma reveals RAS pathway inhibitors as cell-fate hijackers with therapeutic relevance

Rhabdomyosarcoma (RMS) is an aggressive pediatric cancer. Despite robust expression of myogenic regulatory factors, RMS cells are blocked in a proliferative state and do not terminally differentiate. The extent to which the skeletal muscle lineage is represented in RMS tumors and the mechanisms leading to developmental arrest, remain elusive. Here, we used single-cell RNA sequencing (scRNAseq) to resolve RMS subpopulations under basal conditions as well as under genetic perturbation of the fusion protein PAX3:FOXO1 (P3F1). Primary RMS cells were cultured for low number of passages and multiplexed according to Totalseq protocol for single-cell RNA sequencing analysis.