Single-Cell Characterization of Malignant Phenotypes and Developmental Trajectories of Adrenal Neuroblastoma

• Published in: Cancer cell Vol. 38; no. 5; pp. 716 - 733.e6
• Main Authors: Dong, Rui, Yang, Ran, Zhan, Yong, Lai, Hua-Dong, Ye, Chun-Jing, Yao, Xiao-Ying, Luo, Wen-Qin, Cheng, Xiao-Mu, Miao, Ju-Ju, Wang, Jun-Feng, Liu, Bai-Hui, Liu, Xiang-Qi, Xie, Lu-Lu, Li, Yi, Zhang, Man, Chen, Lian, Song, Wei-Chen, Qian, Wei, Gao, Wei-Qiang, Tang, Yun-Hui, Shen, Chun-Yan, Jiang, Wei, Chen, Gong, Yao, Wei, Dong, Kui-Ran, Xiao, Xian-Min, Zheng, Shan, Li, Kai, Wang, Jia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.11.2020
• Subjects: cell differentiation; cell proliferation; cells of origin; chromaffin cells; neural crest cells; neuroblastoma; pediatric cancer; Schwann cell precursors; single-cell RNA sequencing; tumor heterogeneity; single-cell RNA sequencing; neural crest cells; cell differentiation; Schwann cell precursors; chromaffin cells; cell proliferation; neuroblastoma; cells of origin; pediatric cancer; tumor heterogeneity
• ISSN: 1535-6108; 1878-3686; 1878-3686
• DOI: 10.1016/j.ccell.2020.08.014

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. [Display omitted] •The repertoire of normal developing neural-crest-related cells defines the features of NB•NB has a predominant chromaffin-cell-like phenotype•Chromaffin cell differentiation state is highly predictive of patient outcome•MYCN amplification is robustly linked with enhanced EMT NCC-like phenotype Dong et al. provide a detailed phenotypic landscape of human neuroblastoma (NB) using single-cell RNA sequencing and show that the proliferation/differentiation status of developing chromaffin cells is highly associated with the clinical heterogeneity of NB.