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

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 found 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 characterized transcriptome states of NB cells and their dynamics over time and space, and compared 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 identified a list of genes upregulated upon bone marrow involvement and associated with growth dependency, validating the relevance of our multimodal approach.

ORGANISM(S): Homo sapiens

PROVIDER: GSE237881 | GEO | 2024/09/13

REPOSITORIES: GEO

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Neuroblastoma single cell RNA-seq analysis of primary tumour and bone marrow metastases: plasticity, metastatic progression, and intra-patient heterogeneity

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11q deletion or ALK activity curbs DLG2 expression to maintain an undifferentiated state in neuroblastoma.

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