Epigenetic reprogramming drives cellular and phenotypic plasticity in liposarcoma

Single-cell multiomic profiling were performed to characterize the cellular and regulatory heterogeneity of liposarcoma (LPS), including well-differentiated liposarcoma (WDLPS) and de-differentiated liposarcoma (DDLPS), which exhibit markedly different clinical behaviors. Integrated scRNA and scATAC were used to resolve tumor cell states, gene regulatory programs, and tumor microenvironment composition across LPS subtypes. The results reveal distinct differentiation landscapes, with DDLPS enriched for progenitor-like mesenchymal cells, sclerotic WDLPS displaying broader lineage plasticity, and adipocytic WDLPS dominated by terminally differentiated adipocytes. Analysis of the tumor microenvironment further demonstrates differences in immune composition, with DDLPS enriched for immunosuppressive macrophages. Sclerotic WDLPS exhibits intermediate cellular and molecular features between the two subtypes. Together, these datasets provide a comprehensive resource describing the transcriptional, epigenomic, and microenvironmental diversity of liposarcoma.