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 find that implanting human...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53776-3 |
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| author | 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 Valérie Castellani |
| author_facet | 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 Valérie Castellani |
| author_sort | Benjamin Villalard |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8eeee38574194e8a84bc12301a8a48bf |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8eeee38574194e8a84bc12301a8a48bf2024-11-10T12:33:04ZengNature PortfolioNature Communications2041-17232024-11-0115111910.1038/s41467-024-53776-3Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectoryBenjamin Villalard0Arjan Boltjes1Florie Reynaud2Olivier Imbaud3Karine Thoinet4Ilse Timmerman5Séverine Croze6Emy Theoulle7Gianluigi Atzeni8Joël Lachuer9Jan J. Molenaar10Godelieve A. M. Tytgat11Céline Delloye-Bourgeois12Valérie Castellani13Université Claude Bernard Lyon 1, MeLis, CNRS UMR 5284, INSERM U1314, Faculté de Médecine et de Pharmacie - 8 avenue RockefellerPrincess Máxima Center for Pediatric OncologyUniversité Claude Bernard Lyon 1, MeLis, CNRS UMR 5284, INSERM U1314, Faculté de Médecine et de Pharmacie - 8 avenue RockefellerUniversité Claude Bernard Lyon 1, MeLis, CNRS UMR 5284, INSERM U1314, Faculté de Médecine et de Pharmacie - 8 avenue RockefellerUniversité Claude Bernard Lyon 1, MeLis, CNRS UMR 5284, INSERM U1314, Faculté de Médecine et de Pharmacie - 8 avenue RockefellerPrincess Máxima Center for Pediatric OncologyProfileXpert, Claude Bernard Lyon 1 University, SFR santé LYON-EST, UCBL-INSERM US 7-CNRS UMS 3453Université Claude Bernard Lyon 1, MeLis, CNRS UMR 5284, INSERM U1314, Faculté de Médecine et de Pharmacie - 8 avenue RockefellerCellenion SASU – Bioserra 2 - 60 avenue RockefellerProfileXpert, Claude Bernard Lyon 1 University, SFR santé LYON-EST, UCBL-INSERM US 7-CNRS UMS 3453Princess Máxima Center for Pediatric OncologyPrincess Máxima Center for Pediatric OncologyUniversité Claude Bernard Lyon 1, MeLis, CNRS UMR 5284, INSERM U1314, Faculté de Médecine et de Pharmacie - 8 avenue RockefellerUniversité Claude Bernard Lyon 1, MeLis, CNRS UMR 5284, INSERM U1314, Faculté de Médecine et de Pharmacie - 8 avenue RockefellerAbstract 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.https://doi.org/10.1038/s41467-024-53776-3 |
| spellingShingle | 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 Valérie Castellani Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory Nature Communications |
| title | Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory |
| title_full | Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory |
| title_fullStr | Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory |
| title_full_unstemmed | Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory |
| title_short | Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory |
| title_sort | neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory |
| url | https://doi.org/10.1038/s41467-024-53776-3 |
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