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May 4, 2023Nature CommunicationsOpen Access

Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma

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Authors

CTCécile ThirantInsermAPAgathe PeltierInstitut Gustave RoussySDSimon DurandUniversité Claude Bernard Lyon 1

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Implication

Preclinical study uncovers reversible transitions between noradrenergic and mesenchymal states in neuroblastoma, indicating that microenvironmental cues govern tumor cell plasticity.

Key Points

  • To characterize the spontaneous reversibility of noradrenergic and mesenchymal cellular identities and evaluate how the microenvironment influences tumor cell plasticity in neuroblastoma.
  • Assessed spontaneous phenotype switching and epigenetic reprogramming across multiple in vitro neuroblastoma cell line models and in vivo xenografts.
  • Performed single-cell RNA-sequencing on 18 human neuroblastoma tumor biopsies and 15 patient-derived xenograft (PDX) models to evaluate identity profiles in vivo.
  • Neuroblastoma cells displayed spontaneous and reversible transitions between noradrenergic and mesenchymal identities coupled with epigenetic reprogramming.
  • In vivo xenografts derived from either cell identity converged toward a noradrenergic phenotype, demonstrating strong microenvironmental selection pressure.
  • Single-cell RNA-seq confirmed predominant noradrenergic profiles across all 18 patient biopsies and 15 PDX models, while revealing a distinct noradrenergic subpopulation with mesenchymal features.

Cite This Study

Thirant et al. (2023) studied this question.

synapsesocial.com/papers/6a0cd46fa4d785ea816261e3https://doi.org/10.1038/s41467-023-38239-5
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