Cellular origin and clonal evolution of human dedifferentiated liposarcoma.

Humans Liposarcoma / genetics Adipocytes / pathology Clonal Evolution Tumor Microenvironment / genetics Proto-Oncogene Proteins c-mdm2 / metabolism Neoplastic Stem Cells / pathology Single-Cell Analysis Female Cell Dedifferentiation / genetics Male Cell Differentiation / genetics Transforming Growth Factor beta / metabolism Middle Aged Aged

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
12 Sep 2024

Historique:

received: 13 12 2023

accepted: 23 08 2024

medline: 13 9 2024

pubmed: 13 9 2024

entrez: 12 9 2024

Statut: epublish

Résumé

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-β-high immunosuppressive tumor micro-environment.

Identifiants

DOI: 10.1038/s41467-024-52067-1 PMID: 39266532

pubmed: 39266532

doi: 10.1038/s41467-024-52067-1

pii: 10.1038/s41467-024-52067-1

doi:

Substances chimiques

Proto-Oncogene Proteins c-mdm2 EC 2.3.2.27

MDM2 protein, human EC 2.3.2.27

Transforming Growth Factor beta 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

7941

Subventions

Organisme : Fondation ARC pour la Recherche sur le Cancer (ARC Foundation for Cancer Research)

ID : ARCPJA2021060004026

Organisme : Agence Nationale de la Recherche (French National Research Agency)

ID : ANR-10-EQPX-03

Informations de copyright

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