Single-cell transcriptomics and epigenomics unravel the role of monocytes in neuroblastoma bone marrow metastasis

Irfete S. Fetahu (), Wolfgang Esser-Skala, Rohit Dnyansagar, Samuel Sindelar, Fikret Rifatbegovic, Andrea Bileck, Lukas Skos, Eva Bozsaky, Daria Lazic, Lisa Shaw, Marcus Tötzl, Dora Tarlungeanu, Marie Bernkopf, Magdalena Rados, Wolfgang Weninger, Eleni M. Tomazou, Christoph Bock, Christopher Gerner, Ruth Ladenstein, Matthias Farlik, Nikolaus Fortelny () and Sabine Taschner-Mandl ()
Additional contact information
Irfete S. Fetahu: St. Anna Children’s Cancer Research Institute
Wolfgang Esser-Skala: University of Salzburg
Rohit Dnyansagar: University of Salzburg
Samuel Sindelar: University of Salzburg
Fikret Rifatbegovic: St. Anna Children’s Cancer Research Institute
Andrea Bileck: University of Vienna, Department of Analytical Chemistry, Faculty of Chemistry
Lukas Skos: University of Vienna, Department of Analytical Chemistry, Faculty of Chemistry
Eva Bozsaky: St. Anna Children’s Cancer Research Institute
Daria Lazic: St. Anna Children’s Cancer Research Institute
Lisa Shaw: Medical University of Vienna, Department of Dermatology
Marcus Tötzl: St. Anna Children’s Cancer Research Institute
Dora Tarlungeanu: St. Anna Children’s Cancer Research Institute
Marie Bernkopf: St. Anna Children’s Cancer Research Institute
Magdalena Rados: St. Anna Children’s Cancer Research Institute
Wolfgang Weninger: Medical University of Vienna, Department of Dermatology
Eleni M. Tomazou: St. Anna Children’s Cancer Research Institute
Christoph Bock: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Christopher Gerner: University of Vienna, Department of Analytical Chemistry, Faculty of Chemistry
Ruth Ladenstein: St. Anna Children’s Hospital and St. Anna Children’s Cancer Research Institute, Department of Studies and Statistics for Integrated Research and Projects
Matthias Farlik: Medical University of Vienna, Department of Dermatology
Nikolaus Fortelny: University of Salzburg
Sabine Taschner-Mandl: St. Anna Children’s Cancer Research Institute

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Metastasis is the major cause of cancer-related deaths. Neuroblastoma (NB), a childhood tumor has been molecularly defined at the primary cancer site, however, the bone marrow (BM) as the metastatic niche of NB is poorly characterized. Here we perform single-cell transcriptomic and epigenomic profiling of BM aspirates from 11 subjects spanning three major NB subtypes and compare these to five age-matched and metastasis-free BM, followed by in-depth single cell analyses of tissue diversity and cell-cell interactions, as well as functional validation. We show that cellular plasticity of NB tumor cells is conserved upon metastasis and tumor cell type composition is NB subtype-dependent. NB cells signal to the BM microenvironment, rewiring via macrophage mgration inhibitory factor and midkine signaling specifically monocytes, which exhibit M1 and M2 features, are marked by activation of pro- and anti-inflammatory programs, and express tumor-promoting factors, reminiscent of tumor-associated macrophages. The interactions and pathways characterized in our study provide the basis for therapeutic approaches that target tumor-to-microenvironment interactions.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39210-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39210-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39210-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().