| Added by | lklinares |
|---|---|
| Group name | EquipeLL |
| Item Type | Journal Article |
| Title | Cellular origin and clonal evolution of human dedifferentiated liposarcoma |
| Creator | Gruel et al. |
| Author | Nadège Gruel |
| Author | Chloé Quignot |
| Author | Laëtitia Lesage |
| Author | Sophie El Zein |
| Author | Sylvie Bonvalot |
| Author | Dimitri Tzanis |
| Author | Khadija Ait Rais |
| Author | Fabien Quinquis |
| Author | Bastien Manciot |
| Author | Julien Vibert |
| Author | Nadine El Tannir |
| Author | Ahmed Dahmani |
| Author | Héloïse Derrien |
| Author | Didier Decaudin |
| Author | Ivan Bièche |
| Author | Laura Courtois |
| Author | Odette Mariani |
| Author | Laurie Gayte |
| Author | Sylvain Baulande |
| Author | Joshua J. Waterfall |
| Author | Olivier Delattre |
| Author | Sarah Watson |
| Abstract | Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA sequencing, in situ multiplex immunofluorescence and functional assays in paired WD and DD components from primary DDLPS tumors, we characterize the cellular heterogeneity of DDLPS tumor and micro-environment. We identify a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-?-high immunosuppressive tumor micro-environment. |
| Publication | Nature Communications |
| Volume | 15 |
| Issue | 1 |
| Pages | 7941 |
| Date | 2024-09-12 |
| Journal Abbr | Nat Commun |
| Language | eng |
| DOI | 10.1038/s41467-024-52067-1 |
| ISSN | 2041-1723 |
| Library Catalog | PubMed |
| Extra | PMID: 39266532 PMCID: PMC11393420 |
| Tags | Adipocytes, Aged, Cell Dedifferentiation, Cell Differentiation, Clonal Evolution, Female, Humans, Liposarcoma, Male, Middle Aged, Neoplastic Stem Cells, original, Proto-Oncogene Proteins c-mdm2, Single-Cell Analysis, Transforming Growth Factor beta, Tumor Microenvironment |
| Date Added | 2024/12/04 - 08:47:21 |
| Date Modified | 2024/12/04 - 08:47:56 |
| Notes and Attachments | Full Text PDF (Attachment) PubMed entry (Attachment) |
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