Single-cell RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma.
Front Med
; 18(4): 690-707, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-39014137
ABSTRACT
Neuroblastoma (NB) is one of the most common childhood malignancies. Sixty percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor outcomes. However, the molecular mechanisms triggering NB metastasis remain largely uncharacterized. In this study, we generated a transcriptomic atlas of 15 447 NB cells from eight NB samples, including paired samples of primary tumors and bone marrow metastases. We used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common 'starter' subpopulation that initiates tumor development and metastasis. The 'starter' population exhibited high expression levels of multiple cell cycle-related genes, indicating the important role of cell cycle upregulation in NB tumor progression. In addition, our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition (p-EMT) along the metastatic route from the primary site to the bone marrow. Our study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Progressão da Doença
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Análise de Célula Única
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Transição Epitelial-Mesenquimal
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RNA-Seq
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Neuroblastoma
Limite:
Humans
Idioma:
En
Revista:
Front Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China