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

O. C. Bedoya-Reina (), W. Li, M. Arceo, M. Plescher, P. Bullova, H. Pui, M. Kaucka, P. Kharchenko, T. Martinsson, J. Holmberg, I. Adameyko, Qimin Deng, C. Larsson, C. C. Juhlin, P. Kogner and S. Schlisio ()
Additional contact information
O. C. Bedoya-Reina: Karolinska Institutet
W. Li: Karolinska Institutet
M. Arceo: Karolinska Institutet
M. Plescher: Karolinska Institutet
P. Bullova: Karolinska Institutet
H. Pui: Karolinska Institutet
M. Kaucka: Max Planck Institute for Evolutionary Biology
P. Kharchenko: Harvard Medical School
T. Martinsson: Sahlgrenska University Hospital
J. Holmberg: Karolinska Institutet
I. Adameyko: Karolinska Institutet
C. Larsson: Karolinska Institutet
C. C. Juhlin: Karolinska Institutet
P. Kogner: Karolinska Institutet
S. Schlisio: Karolinska Institutet

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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 transcriptome 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.

Date: 2021
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DOI: 10.1038/s41467-021-24870-7

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