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Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory

Benjamin Villalard, Arjan Boltjes, Florie Reynaud, Olivier Imbaud, Karine Thoinet, Ilse Timmerman, Séverine Croze, Emy Theoulle, Gianluigi Atzeni, Joël Lachuer, Jan J. Molenaar, Godelieve A. M. Tytgat, Céline Delloye-Bourgeois () and Valérie Castellani ()
Additional contact information
Benjamin Villalard: Faculté de Médecine et de Pharmacie - 8 avenue Rockefeller
Arjan Boltjes: Princess Máxima Center for Pediatric Oncology
Florie Reynaud: Faculté de Médecine et de Pharmacie - 8 avenue Rockefeller
Olivier Imbaud: Faculté de Médecine et de Pharmacie - 8 avenue Rockefeller
Karine Thoinet: Faculté de Médecine et de Pharmacie - 8 avenue Rockefeller
Ilse Timmerman: Princess Máxima Center for Pediatric Oncology
Séverine Croze: UCBL-INSERM US 7-CNRS UMS 3453
Emy Theoulle: Faculté de Médecine et de Pharmacie - 8 avenue Rockefeller
Gianluigi Atzeni: Cellenion SASU – Bioserra 2 - 60 avenue Rockefeller
Joël Lachuer: UCBL-INSERM US 7-CNRS UMS 3453
Jan J. Molenaar: Princess Máxima Center for Pediatric Oncology
Godelieve A. M. Tytgat: Princess Máxima Center for Pediatric Oncology
Céline Delloye-Bourgeois: Faculté de Médecine et de Pharmacie - 8 avenue Rockefeller
Valérie Castellani: Faculté de Médecine et de Pharmacie - 8 avenue Rockefeller

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Despite their indisputable importance in neuroblastoma (NB) pathology, knowledge of the bases of NB plasticity and heterogeneity remains incomplete. They may be rooted in developmental trajectories of their lineage of origin, the sympatho-adrenal neural crest. We find that implanting human NB cells in the neural crest of the avian embryo allows recapitulating the metastatic sequence until bone marrow involvement. Using deep single cell RNA sequencing, we characterize transcriptome states of NB cells and their dynamics over time and space, and compare them to those of fetal sympatho-adrenal tissues and patient tumors and bone marrow samples. Here we report remarkable transcriptomic proximities restricted to an early sympathetic neuroblast branch that co-exist with phenotypical adaptations over disease progression and recapitulate intratumor and interpatient heterogeneity. Combining avian and patient datasets, we identify a list of genes upregulated during bone marrow involvement and associated with growth dependency, validating the relevance of our multimodal approach.

Date: 2024
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DOI: 10.1038/s41467-024-53776-3

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