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Background <p>Schwannomas are nerve sheath tumors arising at cranial and peripheral nerves, either sporadically or in patients with a schwannomatosis-predisposition syndrome. There is limited understanding of the transcriptional heterogeneity of schwannomas across genetic backgrounds and anatomic locations.</p> Methods <p>Here, we prospectively profile by single-cell full-length transcriptomics tumors from 22 patients with <i>NF2</i>-related schwannomatosis, non-<i>NF2</i>-related schwannomatosis, and sporadic schwannomas, resected from cranial and peripheral nerves. We profiled 11,373 cells&#xa0;(after QC), including neoplastic cells, fibroblasts, T cells, endothelial cells, myeloid cells, and pericytes.</p> Results <p>We characterize the intra-tumoral genetic and transcriptional heterogeneity of schwannoma, identifying six distinct transcriptional metaprograms, with gene signatures related to stress, myelin production, antigen presentation, interferon signaling, glycolysis, and extracellular matrix. We demonstrate the robustness of our findings with analysis of an independent cohort.</p> Conclusions <p>Overall, our atlas describes the spectrum of gene expression across schwannoma entities at the single-cell level and will serve as an important resource for the community.</p>

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A single-cell atlas of Schwannoma across genetic backgrounds and anatomic locations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月11日

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  • L. Nicolas Gonzalez Castro,
  • Avishai Gavish,
  • Lillian Bussema,
  • Christopher W. Mount,
  • Cyril Neftel,
  • Masashi Nomura,
  • E. Antonio Chiocca,
  • Wenya Linda Bi,
  • Omar Arnaout,
  • Fred G. Barker II,
  • Justin M. Brown,
  • Justin T. Jordan,
  • Tracy T. Batchelor,
  • Anat Stemmer-Rachamimov,
  • Scott R. Plotkin,
  • Itay Tirosh,
  • Mario L. Suvà

摘要

Background

Schwannomas are nerve sheath tumors arising at cranial and peripheral nerves, either sporadically or in patients with a schwannomatosis-predisposition syndrome. There is limited understanding of the transcriptional heterogeneity of schwannomas across genetic backgrounds and anatomic locations.

Methods

Here, we prospectively profile by single-cell full-length transcriptomics tumors from 22 patients with NF2-related schwannomatosis, non-NF2-related schwannomatosis, and sporadic schwannomas, resected from cranial and peripheral nerves. We profiled 11,373 cells (after QC), including neoplastic cells, fibroblasts, T cells, endothelial cells, myeloid cells, and pericytes.

Results

We characterize the intra-tumoral genetic and transcriptional heterogeneity of schwannoma, identifying six distinct transcriptional metaprograms, with gene signatures related to stress, myelin production, antigen presentation, interferon signaling, glycolysis, and extracellular matrix. We demonstrate the robustness of our findings with analysis of an independent cohort.

Conclusions

Overall, our atlas describes the spectrum of gene expression across schwannoma entities at the single-cell level and will serve as an important resource for the community.