Cellular origin and clonal evolution of human dedifferentiated liposarcoma

• DOI: 10.1038/s41467-024-52067-1
• Publication Date: 2024-09-16T18:03:50Z
• Authors: Nadège Gruel; Chloé Quignot; Laëtitia Lesage; Sophie El Zein; Sylvie Bonvalot; Dimitri Tzanis; Khadija Ait Rais; Fabien Quinquis; Bastien Manciot; Julien Vibert; Nadine El Tannir; Ahmed Dahmani; Héloïse Derrien; Didier Decaudin; Ivan Bièche; Laura Courtois; Odette Mariani; Laëtitia K. Linares; Laurie Gayte; Sylvain Baulande; Joshua J. Waterfall; Olivier Delattre; Gaëlle Pierron; Sarah Watson
• Keywords: Male; Science; Q; Proto-Oncogene Proteins c-mdm2; Cell Differentiation; Liposarcoma; Cell Dedifferentiation; Middle Aged; Article; Clonal Evolution; Transforming Growth Factor beta; Adipocytes; Tumor Microenvironment; Neoplastic Stem Cells; Humans; Female; Single-Cell Analysis; Aged

Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It characterized by a component of undifferentiated tumor cells coexisting with well-differentiated adipocytic cells. Both dedifferentiated (DD) and (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA in situ multiplex immunofluorescence functional assays paired WD DD from primary DDLPS tumors, we characterize heterogeneity micro-environment. We identify population adipocyte stem (ASC) showing striking similarities stromal progenitors found white adipose tissue. show that ASC harbor ancestral genomic alterations components, suggesting both derive these following clonal evolution. Last, keep important biological properties including pluripotency adipogenic are inhibited TGF-β-high immunosuppressive