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Updated: Jul 5, 2025

Preparation of Tunable Extracellular Matrix Microenvironments to Evaluate Schwann Cell Phenotype Specification
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Preparation of Tunable Extracellular Matrix Microenvironments to Evaluate Schwann Cell Phenotype Specification

Published on: June 2, 2020

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Epigenetic reprogramming shapes the cellular landscape of schwannoma

S John Liu1,2,3,4, Tim Casey-Clyde1,2,3, Nam Woo Cho1,5

  • 1Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.

Nature Communications
|January 12, 2024
PubMed

Insights

Epigenetic reprogramming drives schwannoma cell states and tumor immunity. Radiotherapy induces schwannoma cell interconversion via epigenetic and metabolic changes, impacting the tumor microenvironment.

Area of Science:

  • Oncology
  • Neuroscience
  • Epigenetics

Background:

  • Mechanisms of cancer cell states and therapy response remain unclear.
  • Schwannomas, common peripheral nervous system tumors, present an opportunity to study these mechanisms.
  • Understanding tumor evolution and immune microenvironment is crucial for effective cancer treatment.

Purpose of the Study:

  • To investigate how epigenetic reprogramming shapes schwannoma cellular states.
  • To identify molecular groups within schwannomas and their relation to tumor microenvironment.
  • To explore the impact of radiotherapy on schwannoma cell states and immune microenvironment.

Main Methods:

  • Developed a novel technique for simultaneous single-nucleus chromatin accessibility and gene expression analysis.
  • Integrated genetic and therapeutic perturbations with multi-omic single-nucleus profiling.
  • Analyzed molecular subgroups of schwannomas based on pathway activation.

Main Results:

  • Identified two distinct molecular groups of schwannomas linked to neural crest or nerve injury pathways.
  • Demonstrated that radiotherapy can reprogram neural crest schwannomas into immune-enriched schwannomas.
  • Revealed epigenetic and metabolic reprogramming as key mediators of this interconversion and immune microenvironment shaping.

Conclusions:

  • Epigenetic reprogramming is a fundamental driver of schwannoma cellular diversity and evolution.
  • Radiotherapy induces significant epigenetic and metabolic changes in schwannoma cells, altering the tumor immune microenvironment.
  • Established a framework for understanding epigenetic control of tumor plasticity and response to therapy.

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