Single-cell Transcriptomics and Epigenomics Unravel the Role of Monocytes in Neuroblastoma Bone Marrow Metastasis

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Jun 26

PMID 37365178

Authors

Irfete S Fetahu

Wolfgang Esser-Skala

Rohit Dnyansagar

Samuel Sindelar

Fikret Rifatbegovic

Andrea Bileck

Lukas Skos

Eva Bozsaky

Daria Lazic

Lisa Shaw

Marcus Totzl

Dora Tarlungeanu

Marie Bernkopf

Magdalena Rados

Wolfgang Weninger

Eleni M Tomazou

Christoph Bock

Christopher Gerner

Ruth Ladenstein

Matthias Farlik

Nikolaus Fortelny

Sabine Taschner-Mandl

Affiliations

Soon will be listed here.

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.

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