Nature Communications (May 2023)
Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma
- Cécile Thirant,
- Agathe Peltier,
- Simon Durand,
- Amira Kramdi,
- Caroline Louis-Brennetot,
- Cécile Pierre-Eugène,
- Margot Gautier,
- Ana Costa,
- Amandine Grelier,
- Sakina Zaïdi,
- Nadège Gruel,
- Irène Jimenez,
- Eve Lapouble,
- Gaëlle Pierron,
- Déborah Sitbon,
- Hervé J. Brisse,
- Arnaud Gauthier,
- Paul Fréneaux,
- Sandrine Grossetête,
- Laura G. Baudrin,
- Virginie Raynal,
- Sylvain Baulande,
- Angela Bellini,
- Jaydutt Bhalshankar,
- Angel M. Carcaboso,
- Birgit Geoerger,
- Hermann Rohrer,
- Didier Surdez,
- Valentina Boeva,
- Gudrun Schleiermacher,
- Olivier Delattre,
- Isabelle Janoueix-Lerosey
Affiliations
- Cécile Thirant
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Agathe Peltier
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Simon Durand
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Amira Kramdi
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Caroline Louis-Brennetot
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Cécile Pierre-Eugène
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Margot Gautier
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Ana Costa
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Amandine Grelier
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Sakina Zaïdi
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Nadège Gruel
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Irène Jimenez
- SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie
- Eve Lapouble
- Institut Curie, Unité de Génétique Somatique
- Gaëlle Pierron
- Institut Curie, Unité de Génétique Somatique
- Déborah Sitbon
- Institut Curie, Unité de Génétique Somatique
- Hervé J. Brisse
- Institut Curie, Department of Imaging, PSL Research University
- Arnaud Gauthier
- Institut Curie, Department of Biopathology
- Paul Fréneaux
- Institut Curie, Department of Biopathology
- Sandrine Grossetête
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Laura G. Baudrin
- Institut Curie, Genomics of Excellence (ICGex) Platform, Paris, France. Institut Curie, Single Cell Initiative
- Virginie Raynal
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Sylvain Baulande
- Institut Curie, Genomics of Excellence (ICGex) Platform, Paris, France. Institut Curie, Single Cell Initiative
- Angela Bellini
- SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie
- Jaydutt Bhalshankar
- SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie
- Angel M. Carcaboso
- SJD Pediatric Cancer Center Barcelona, Institut de Recerca Sant Joan de Déu
- Birgit Geoerger
- Gustave Roussy Cancer Campus, INSERM U1015, Department of Pediatric and Adolescent Oncology, Université Paris-Saclay
- Hermann Rohrer
- Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Neuroscience Center, Goethe University
- Didier Surdez
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Valentina Boeva
- Inserm, U1016, Cochin Institute, CNRS UMR8104, Paris University
- Gudrun Schleiermacher
- SIREDO: Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer, Institut Curie
- Olivier Delattre
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- Isabelle Janoueix-Lerosey
- Institut Curie, Inserm U830, PSL Research University, Diversity and Plasticity of Childhood Tumors Lab
- DOI
- https://doi.org/10.1038/s41467-023-38239-5
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 18
Abstract
Abstract Noradrenergic and mesenchymal identities have been characterized in neuroblastoma cell lines according to their epigenetic landscapes and core regulatory circuitries. However, their relationship and relative contribution in patient tumors remain poorly defined. We now document spontaneous and reversible plasticity between the two identities, associated with epigenetic reprogramming, in several neuroblastoma models. Interestingly, xenografts with cells from each identity eventually harbor a noradrenergic phenotype suggesting that the microenvironment provides a powerful pressure towards this phenotype. Accordingly, such a noradrenergic cell identity is systematically observed in single-cell RNA-seq of 18 tumor biopsies and 15 PDX models. Yet, a subpopulation of these noradrenergic tumor cells presents with mesenchymal features that are shared with plasticity models, indicating that the plasticity described in these models has relevance in neuroblastoma patients. This work therefore emphasizes that intrinsic plasticity properties of neuroblastoma cells are dependent upon external cues of the environment to drive cell identity.
