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Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in DSRCTs.
Henon, Clémence; Vibert, Julien; Eychenne, Thomas; Gruel, Nadège; Colmet-Daage, Léo; Ngo, Carine; Garrido, Marlène; Dorvault, Nicolas; Marques Da Costa, Maria Eugenia; Marty, Virginie; Signolle, Nicolas; Marchais, Antonin; Herbel, Noé; Kawai-Kawachi, Asuka; Lenormand, Madison; Astier, Clémence; Chabanon, Roman; Verret, Benjamin; Bahleda, Rastislav; Le Cesne, Axel; Mechta-Grigoriou, Fatima; Faron, Matthieu; Honoré, Charles; Delattre, Olivier; Waterfall, Joshua J; Watson, Sarah; Postel-Vinay, Sophie.
Afiliación
  • Henon C; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, France; Drug Development Department, DITEP, Gustave Roussy, Villejuif, France.
  • Vibert J; INSERM U830, Équipe labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France; INSERM U830, Integrative Functional Genomics of Cancer Lab, PSL Research University, Institut Curie Research Center,
  • Eychenne T; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Gruel N; INSERM U830, Équipe labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France; Department of Translational Research, PSL Research University, Institut Curie Research Center, Paris, France.
  • Colmet-Daage L; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Ngo C; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France; Department of Pathology, Gustave Roussy, Villejuif, France.
  • Garrido M; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Dorvault N; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Marques Da Costa ME; INSERM U1015, Gustave Roussy, Paris Saclay University, Villejuif, France; Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.
  • Marty V; Experimental and Translational Pathology Platform (PETRA), AMMICa, INSERM US23/UAR3655, Gustave Roussy, Villejuif, France.
  • Signolle N; Experimental and Translational Pathology Platform (PETRA), AMMICa, INSERM US23/UAR3655, Gustave Roussy, Villejuif, France.
  • Marchais A; INSERM U1015, Gustave Roussy, Paris Saclay University, Villejuif, France; Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.
  • Herbel N; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Kawai-Kawachi A; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Lenormand M; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Astier C; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Chabanon R; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France.
  • Verret B; Department of Medical Oncology, Gustave Roussy, Villejuif, France; Breast Cancer Translational Research Group, INSERM U981, Gustave Roussy, Villejuif, France.
  • Bahleda R; Drug Development Department, DITEP, Gustave Roussy, Villejuif, France.
  • Le Cesne A; Department of Medical Oncology, Gustave Roussy, Villejuif, France; International Department of Medical Oncology, Gustave Roussy, Villejuif, France.
  • Mechta-Grigoriou F; INSERM U830, Equipe labellisée LNCC, Stress et Cancer, PSL Research University, Institut Curie Research Center, Paris, France.
  • Faron M; Surgery Department, Gustave Roussy, Villejuif, France.
  • Honoré C; Surgery Department, Gustave Roussy, Villejuif, France.
  • Delattre O; INSERM U830, Équipe labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France.
  • Waterfall JJ; INSERM U830, Integrative Functional Genomics of Cancer Lab, PSL Research University, Institut Curie Research Center, Paris, France; Department of Translational Research, PSL Research University, Institut Curie Research Center, Paris, France.
  • Watson S; INSERM U830, Équipe labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, SIREDO Oncology Center, Institut Curie Research Center, Paris, France; Department of Translational Research, PSL Research University, Institut Curie Research Center, Paris, France.
  • Postel-Vinay S; ATIP-Avenir INSERM and ERC StG Group, Equipe labellisée ARC Recherche Fondamentale, INSERM U981, Gustave Roussy, Paris Saclay University, Villejuif, France; Drug Development Department, DITEP, Gustave Roussy, Villejuif, France; University College of London, Cancer Institute, London, UK. Electronic a
Cell Rep Med ; 5(6): 101582, 2024 Jun 18.
Article en En | MEDLINE | ID: mdl-38781959
ABSTRACT
Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on 12 samples from five patients, we find that DSRCT tumor cells cluster into consistent subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs. In vitro modeling shows that high EWSR1WT1 DNA-binding activity associates with most lineage-related states, in contrast to glycolytic and profibrotic states. Single-cell chromatin accessibility analysis suggests that EWSR1WT1 binding site variability may drive distinct lineage-related transcriptional programs, supporting some level of cell-intrinsic plasticity. Spatial transcriptomics reveals that glycolytic and profibrotic states specifically localize within hypoxic niches at the periphery of tumor cell islets, suggesting an additional role of tumor cell-extrinsic microenvironmental cues. We finally identify a single-cell transcriptomics-derived epithelial signature associated with improved patient survival, highlighting the clinical relevance of our findings.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Análisis de la Célula Individual / Microambiente Tumoral Límite: Female / Humans / Male Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Análisis de la Célula Individual / Microambiente Tumoral Límite: Female / Humans / Male Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos