Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.

神经母细胞瘤 (NB) 是神经嵴源性恶性肿瘤的一种亚型，是儿童期最常见的颅外实体瘤。尽管进行了广泛的研究，但 NB 的潜在发育起源仍不清楚。使用单细胞 RNA 测序，我们从 16 名患者的 160,910 个细胞中生成肾上腺 NB 的转录组，并从相对较晚发育阶段的早期人类胚胎和胎儿肾上腺的 12,103 个细胞中生成 NB 起源的推定发育细胞的转录组。我们发现大多数肾上腺 NB 肿瘤细胞在转录上反映了去甲肾上腺素能嗜铬细胞。恶性状态也概括了正常发育过程中嗜铬细胞的增殖/分化状态。