Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors

Abstract Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes different clinical risk groups stages, including healthy adrenal gland. We compare tumor cell populations embryonic mouse sympatho-adrenal derivatives, post-natal human provide evidence that low high-risk have identities, representing two disease entities. Low-risk presents transcriptome resembles sympatho- chromaffin cells, whereas malignant cells enriched subtype TRKB+ cholinergic progenitor population identified Analyses these reveal gene expression programs for worst better survival correlation age diagnosis. Our findings cellular identities composition tumors reflecting heterogeneity