Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
Single-cell analyses of metastatic bone marrow in human neuroblastoma reveals microenvironmental remodeling and metastatic signature
Shenglin Mei, … , Per Kogner, Ninib Baryawno
Shenglin Mei, … , Per Kogner, Ninib Baryawno
Published February 15, 2024
Citation Information: JCI Insight. 2024;9(6):e173337. https://doi.org/10.1172/jci.insight.173337.
View: Text | PDF
Resource and Technical Advance Bone biology Oncology

Single-cell analyses of metastatic bone marrow in human neuroblastoma reveals microenvironmental remodeling and metastatic signature

  • Text
  • PDF
Abstract

Neuroblastoma is an aggressive pediatric cancer with a high rate of metastasis to the BM. Despite intensive treatments including high-dose chemotherapy, the overall survival rate for children with metastatic neuroblastoma remains dismal. Understanding the cellular and molecular mechanisms of the metastatic tumor microenvironment is crucial for developing new therapies and improving clinical outcomes. Here, we used single-cell RNA-Seq to characterize immune and tumor cell alterations in neuroblastoma BM metastases by comparative analysis with patients without metastases. Our results reveal remodeling of the immune cell populations and reprogramming of gene expression profiles in the metastatic niche. In particular, within the BM metastatic niche, we observed the enrichment of immune cells, including tumor-associated neutrophils, macrophages, and exhausted T cells, as well as an increased number of Tregs and a decreased number of B cells. Furthermore, we highlighted cell communication between tumor cells and immune cell populations, and we identified prognostic markers in malignant cells that are associated with worse clinical outcomes in 3 independent neuroblastoma cohorts. Our results provide insight into the cellular, compositional, and transcriptional shifts underlying neuroblastoma BM metastases that contribute to the development of new therapeutic strategies.

Authors

Shenglin Mei, Adele M. Alchahin, Bethel Tesfai Embaie, Ioana Maria Gavriliuc, Bronte Manouk Verhoeven, Ting Zhao, Xiangyun Li, Nathan Elias Jeffries, Adena Pepich, Hirak Sarkar, Thale Kristin Olsen, Malin Wickström, Jakob Stenman, Oscar Reina-Bedoya, Peter V. Kharchenko, Philip J. Saylor, John Inge Johnsen, David B. Sykes, Per Kogner, Ninib Baryawno

×

Figure 2

Myeloid cells characterization, enrichment, and differentiation trajectory.

Options: View larger image (or click on image) Download as PowerPoint
Myeloid cells characterization, enrichment, and differentiation trajecto...
(A) Joint embedding represent the detailed annotation of myeloid cell subpopulations. (B) Dot plot demonstrating marker gene expression across different myeloid subpopulations. The color represents scaled average expression of marker genes in each cell type, and the size indicates the proportion of cells expressing marker genes. (C) Comparison of Neutrohil-1 and Neutrohil-2 proportion in NB bone metastatic (n = 7) and NB bone nonmetastatic (n = 7) samples. Statistics are accessed with 2-sided Wilcoxon ranked-sum test (*P < 0.05). For box plots, the center line represents the median, box limits represent upper and lower quartiles, and whiskers depicts 1.5 × the interquartile range (IQR). (D) UMAP embedding showing representative gene expression for neutrophiles. (E) Violin plot showing representative marker gene expression for 2 neutrophil subpopulations. (F) Estimated trajectory tree moving from promyeloid cells to Neutrophil-1 and Neutrophil-2 (top). Trajectory analysis demonstrates MKI67, CAMP, VNN2, and CMTM2 expression across pseudotime (bottom). (G) Heatmap showing the gene expression dynamics with pseudotime. Representative genes are shown for each cellular state along the cell differentiation. (H) Joint alignment of myeloid cells from NB bone metastatic tumor and NB primary tumor, visualized in UMAP embedding. (I) DEGs of macrophage comparing NB bone metastatic tumor with NB primary tumor, shown as volcano plot. The vertical dashed lines show the cut-off for gene filtering (log2FC 2 and −2), and the horizontal dashed lines signify adjusted P values of 0.01. (J) Enriched GO terms for DEGs from I. The statistical analysis was done using a hypergeometric test.

Copyright © 2025 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts