1. Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory.
- Author
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Villalard B, Boltjes A, Reynaud F, Imbaud O, Thoinet K, Timmerman I, Croze S, Theoulle E, Atzeni G, Lachuer J, Molenaar JJ, Tytgat GAM, Delloye-Bourgeois C, and Castellani V
- Subjects
- Humans, Animals, Chick Embryo, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Neoplasm Metastasis, Single-Cell Analysis, Sympathetic Nervous System pathology, Sympathetic Nervous System metabolism, Bone Marrow pathology, Bone Marrow metabolism, Gene Expression Profiling, Neuroblastoma pathology, Neuroblastoma genetics, Neuroblastoma metabolism, Transcriptome, Neural Crest metabolism, Neural Crest pathology, Disease Progression
- 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., (© 2024. The Author(s).)
- Published
- 2024
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