Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development

We analyzed the transcriptomic features of spontaneous regression in pre-cancerous neuroblasts using Th-MYCN mice, an animal model that closely resembles human neuroblastoma. Single-cell transcriptomic analysis of ganglion tissues from Th-MYCN mice was conducted to elucidate the cellular and molecular underpinnings. Trajectory analysis of pre-cancerous neuroblasts revealed a distinct subtype we designated as "uncommitted" cells, characterized by the expression of neuronal genes, indicative of a semi-differentiated state. Samples with predicted failed tumorigenesis had a greater proportion of these uncommitted cells, hinting at their association with spontaneous regression. Overall design: To investigate the cellular and molecular mechanisms underlying the fate determination of neuroblastoma cells in Th-MYCN+/-mice, we performed scRNA-seq of SMG tissues from 3-week-old wild-type (WT, n = 1), 3-week-old Th-MYCN+/- (n = 10), and 6-week-old Th-MYCN+/- mice (n = 1)