Journal article
Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma
Nature genetics
25/Mar/2021
PMID: 33767450
Abstract
Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system. However, the cellular origin of neuroblastoma has yet to be defined. Here we studied the single-cell transcriptomes of neuroblastomas and normal human developing adrenal glands at various stages of embryonic and fetal development. We defined normal differentiation trajectories from Schwann cell precursors over intermediate states to neuroblasts or chromaffin cells and showed that neuroblastomas transcriptionally resemble normal fetal adrenal neuroblasts. Importantly, neuroblastomas with varying clinical phenotypes matched different temporal states along normal neuroblast differentiation trajectories, with the degree of differentiation corresponding to clinical prognosis. Our work highlights the roles of oncogenic MYCN and loss of TFAP2B in blocking differentiation and may provide the basis for designing therapeutic interventions to overcome differentiation blocks.
Details
- Title
- Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma
- Creators
- Selina Jansky - Heidelberg UniversityAshwini Kumar Sharma - Health Data Science Unit, Medical Faculty University Heidelberg and BioQuant, Heidelberg, GermanyVerena Körber - German Cancer Research CenterAndrés Quintero - Health Data Science Unit, Medical Faculty University Heidelberg and BioQuant, Heidelberg, GermanyUmut H Toprak - Division of Neuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, GermanyElisa M Wecht - Division of Neuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, GermanyMoritz Gartlgruber - Division of Neuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, GermanyAlessandro Greco - Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ), Heidelberg, GermanyElad Chomsky - 972WIS_INST___83Thomas G P Grünewald - Institute of Pathology, Heidelberg University Hospital, Heidelberg, GermanyKai-Oliver Henrich - Division of Neuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, GermanyAmos Tanay - 972WIS_INST___83Carl Herrmann - Health Data Science Unit, Medical Faculty University Heidelberg and BioQuant, Heidelberg, GermanyThomas Höfer - Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ), Heidelberg, GermanyFrank Westermann (Corresponding Author) - German Cancer Research Center
- Resource Type
- Journal article
- Publication Details
- Nature genetics; 25/Mar/2021
- Number of pages
- 30
- Publisher
- United States
- Language
- English
- DOI
- https://doi.org/10.1038/s41588-021-00806-1
- PMID
- 33767450
- Grant note
- We thank the patients and their parents for making available the tumor specimens analyzed in this study. We also thank the German Neuroblastoma Biobank for providing these samples. The human embryonic and fetal materials were provided by the joint MRC/Wellcome Trust (grant no. MR/R006237/1) Human Developmental Biology Resource (www.hdbr.org). The institutional review board approved the collection and use of all specimens in this study. We thank J.-P. Mallm and the Single-cell Open Lab, Genomics and Proteomics Core Facility and Light Microscopy Facility at the German Cancer Research Center. The results published in this article are in part based on data generated by the Therapeutically Applicable Research to Generate Effective Treatments (https://ocg.cancer.gov/programs/target) initiative (phs000218). The data used for this analysis are available at https://portal.gdc.cancer.gov/projects. This work was supported by the Fördergesellschaft Kinderkrebs-Neuroblastom-Forschung e.V. (F.W. and S.J.), German-Israeli Helmholtz Research School in Cancer Biology (S.J.), German Ministry of Science and Education (e:Med initiative, grant no. 01ZX1307 to F.W.; grant no. 031L0238 to F.W. and T.H.), EU as part of the EraCoSysMed initiative (Optimize-NB and Infer-NB to F.W. and T. H.), German Cancer Research Center intramural program for interaction projects (Single-cell Open Lab) and DKFZ-Heidelberg Center for Personalized Oncology (HIPO) and National Center for Tumor Disease (NCT 3.0—ENHANCE to F.W.). The laboratory of T.G.P.G. is supported by the Barbara & Wilfried Mohr Foundation.
- Record Identifier
- 993260817703596
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