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

• DOI: 10.1016/j.ccell.2020.08.014
• Publication Date: 2020-09-17T14:51:30Z
• Authors: Rui Dong; Ran Yang; Yong Zhan; Hua-Dong Lai; Chun-Jing Ye; Xiao-Ying Yao; Wen-Qin Luo; Xiao-Mu Cheng; Ju-Ju Miao; Jun-Feng Wang; Bai-Hui Liu; Xiang-Qi Liu; Lu-Lu Xie; Yi Li; Man Zhang; Lian Chen; Wei-Chen Song; Wei Qian; Wei-Qiang Gao; Yun-Hui Tang; Chun-Yan Shen; Wei Jiang; Gong Chen; Wei Yao; Kui-Ran Dong; Xian-Min Xiao; Shan Zheng; Kai Li; Jia Wang
• Keywords: Developmental Biology

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.