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Nat Commun ; 12(1): 5309, 2021 09 07.
Article in English | MEDLINE | ID: mdl-34493726

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.


Subject(s)
Adrenal Gland Neoplasms/genetics , Adrenal Glands/metabolism , Membrane Glycoproteins/genetics , Neoplasm Proteins/genetics , Neuroblastoma/genetics , Receptor, trkB/genetics , Transcriptome , Adrenal Gland Neoplasms/metabolism , Adrenal Gland Neoplasms/mortality , Adrenal Gland Neoplasms/pathology , Adrenal Glands/pathology , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Differentiation , Cell Nucleus/genetics , Cell Nucleus/metabolism , Child, Preschool , Chromaffin Cells/metabolism , Chromaffin Cells/pathology , Early Diagnosis , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Male , Membrane Glycoproteins/metabolism , Mice , Neoplasm Proteins/classification , Neoplasm Proteins/metabolism , Neuroblastoma/metabolism , Neuroblastoma/mortality , Neuroblastoma/pathology , Receptor, trkB/metabolism , Risk Assessment , Single-Cell Analysis , Species Specificity , Survival Analysis
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