神经母细胞瘤（NB）是最常见的儿童恶性肿瘤之一。百分之六十的患者在诊断时表现出广泛传播的临床症状，并且结果不佳。然而，引发 NB 转移的分子机制在很大程度上仍不清楚。在这项研究中，我们从 8 个 NB 样本中生成了 15 447 个 NB 细胞的转录组图谱，其中包括原发肿瘤和骨髓转移瘤的配对样本。我们使用时间分辨分析来绘制同一患者中 NB 细胞从原发肿瘤到转移灶的进化轨迹，并确定了启动肿瘤发展和转移的常见“起始”亚群。 “起始”群体表现出多个细胞周期相关基因的高表达水平，表明细胞周期上调在 NB 肿瘤进展中的重要作用。此外，我们的进化轨迹分析表明，从原发部位到骨髓的转移途径涉及部分上皮间质转化（p-EMT）。我们的研究提供了对驱动 NB 转移的程序的见解，并提出了转移起始细胞的特征作为独立的预后指标和抑制 NB 转移起始的潜在治疗靶标。© 2024。高等教育出版社。

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.© 2024. Higher Education Press.