Wellcome Sanger Institute, CB10 1SA Hinxton, UK.
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, Netherlands.
Sci Adv. 2021 Feb 5;7(6). doi: 10.1126/sciadv.abd3311. Print 2021 Feb.
Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer ( = 19,723) with normal fetal adrenal single-cell transcriptomes ( = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.
神经母细胞瘤是一种儿童癌症，类似于神经嵴的发育阶段。尚未确定神经母细胞瘤癌细胞代表哪些发育过程。在这里，我们通过比较癌症（= 19723）和正常胎儿肾上腺单细胞转录组（= 57972）来试图揭示神经母细胞瘤癌细胞的表型。我们的主要发现是神经母细胞瘤癌细胞类似于胎儿交感母细胞，但不是其他胎儿肾上腺细胞类型。交感母细胞状态是神经母细胞瘤细胞的普遍特征，超越了细胞簇的多样性、个体患者和临床表型。我们在 650 个神经母细胞瘤批量转录组中证实了我们的发现，并将神经母细胞瘤基因组的典型特征与转录信号相结合。总的来说，我们的观察表明存在一种泛神经母细胞瘤癌细胞状态，这可能对新的免疫治疗和靶向途径具有吸引力。
