Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors [ATAC-seq]

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs. ATAC-seq was performed in the JN-DSRCT-1 cell line after a 48-hour siRNA-mediated silencing using a control non-targeting siRNA, a CCND1-targeting siRNA, a EWSR1::WT1 siRNA, or in a control condition without transfection.