NBAtlas: A harmonized single-cell transcriptomic reference atlas of human neuroblastoma tumors

Noah Bonine; Vittorio Zanzani; Annelies Van Hemelryk; Bavo Vanneste; Christian Zwicker; Tinne Thoné; Sofie Roelandt; Sarah-Lee Bekaert; Jan Koster; Isabelle Janoueix-Lerosey; Cécile Thirant; Stéphane Van Haver; Stephen S Roberts; Liselot M Mus; Bram De Wilde; Nadine Van Roy; Celine Everaert; Frank Speleman; Vanessa Vermeirssen; Charlotte L Scott; Katleen De Preter

doi:10.1016/j.celrep.2024.114804

NBAtlas: A harmonized single-cell transcriptomic reference atlas of human neuroblastoma tumors

Cell Rep. 2024 Oct 22;43(10):114804. doi: 10.1016/j.celrep.2024.114804. Epub 2024 Oct 3.

Authors

Noah Bonine¹, Vittorio Zanzani², Annelies Van Hemelryk³, Bavo Vanneste⁴, Christian Zwicker⁴, Tinne Thoné⁴, Sofie Roelandt¹, Sarah-Lee Bekaert⁵, Jan Koster⁶, Isabelle Janoueix-Lerosey⁷, Cécile Thirant⁷, Stéphane Van Haver⁸, Stephen S Roberts⁹, Liselot M Mus⁵, Bram De Wilde⁵, Nadine Van Roy⁵, Celine Everaert¹, Frank Speleman⁵, Vanessa Vermeirssen¹⁰, Charlotte L Scott¹¹, Katleen De Preter¹²

Affiliations

¹ Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; VIB-UGent Center for Medical Biotechnology, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
² Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; VIB-UGent Center for Medical Biotechnology, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Laboratory for Computational Biology, Integromics and Gene Regulation (CBIGR), Ghent University, Ghent, Belgium.
³ Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052 Ghent, Belgium.
⁴ Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052 Ghent, Belgium.
⁵ Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
⁶ Amsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, the Netherlands.
⁷ Inserm U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France.
⁸ Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Tow Center for Developmental Oncology, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁹ Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA.
¹⁰ Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Laboratory for Computational Biology, Integromics and Gene Regulation (CBIGR), Ghent University, Ghent, Belgium.
¹¹ Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052 Ghent, Belgium. Electronic address: [email protected].
¹² Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; VIB-UGent Center for Medical Biotechnology, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium. Electronic address: [email protected].

PMID: 39368085
DOI: 10.1016/j.celrep.2024.114804

Abstract

Neuroblastoma, a rare embryonic tumor arising from neural crest development, is responsible for 15% of pediatric cancer-related deaths. Recently, several single-cell transcriptome studies were performed on neuroblastoma patient samples to investigate the cell of origin and tumor heterogeneity. However, these individual studies involved a small number of tumors and cells, limiting the conclusions that could be drawn. To overcome this limitation, we integrated seven single-cell or single-nucleus datasets into a harmonized cell atlas covering 362,991 cells across 61 patients. We use this atlas to decipher the transcriptional landscape of neuroblastoma at single-cell resolution, revealing associations between transcriptomic profiles and clinical outcomes within the tumor compartment. In addition, we characterize the complex immune-cell landscape and uncover considerable heterogeneity among tumor-associated macrophages. Finally, we showcase the utility of our atlas as a resource by expanding it with additional data and using it as a reference for data-driven cell-type annotation.

Keywords: CP: Cancer; NBAtlas; atlas; integration; neuroblastoma; reference; single cell; single nucleus; transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Neuroblastoma* / genetics
Neuroblastoma* / metabolism
Neuroblastoma* / pathology
Single-Cell Analysis* / methods
Transcriptome* / genetics