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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 of neuroblastoma with
different clinical risk groups and stages, including healthy adrenal gland. We compare tumor
cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human
adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell
identities, representing two disease entities. Low-risk neuroblastoma presents a tran-
scriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched
in high-risk neuroblastoma resembles a subtype of TRKB+cholinergic progenitor population
identified in human post-natal gland. Analyses of these populations reveal different gene
expression programs for worst and better survival in correlation with age at diagnosis. Our
findings reveal two cellular identities and a composition of human neuroblastoma tumors
reflecting clinical heterogeneity and outcome.
