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
Affiliations
Noah Bonine
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
Vittorio Zanzani
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
Annelies Van Hemelryk
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
Bavo Vanneste
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
Christian Zwicker
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
Tinne Thoné
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
Sofie Roelandt
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
Sarah-Lee Bekaert
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
Jan Koster
Amsterdam UMC Location University of Amsterdam, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam, the Netherlands
Isabelle Janoueix-Lerosey
Inserm U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France
Cécile Thirant
Inserm U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France
Stéphane Van Haver
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
Stephen S. Roberts
Department of Pediatrics, Oregon Health & Science University, Portland, OR, USA
Liselot M. Mus
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
Bram De Wilde
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
Nadine Van Roy
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
Celine Everaert
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
Frank Speleman
Department of Biomolecular Medicine, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium
Vanessa Vermeirssen
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
Charlotte L. Scott
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; Corresponding author
Katleen De Preter
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; Corresponding author
Summary: 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.
