Nature Communications (Jan 2024)
Epigenetic reprogramming shapes the cellular landscape of schwannoma
- S. John Liu,
- Tim Casey-Clyde,
- Nam Woo Cho,
- Jason Swinderman,
- Melike Pekmezci,
- Mark C. Dougherty,
- Kyla Foster,
- William C. Chen,
- Javier E. Villanueva-Meyer,
- Danielle L. Swaney,
- Harish N. Vasudevan,
- Abrar Choudhury,
- Joanna Pak,
- Jonathan D. Breshears,
- Ursula E. Lang,
- Charlotte D. Eaton,
- Kamir J. Hiam-Galvez,
- Erica Stevenson,
- Kuei-Ho Chen,
- Brian V. Lien,
- David Wu,
- Steve E. Braunstein,
- Penny K. Sneed,
- Stephen T. Magill,
- Daniel Lim,
- Michael W. McDermott,
- Mitchel S. Berger,
- Arie Perry,
- Nevan J. Krogan,
- Marlan R. Hansen,
- Matthew H. Spitzer,
- Luke Gilbert,
- Philip V. Theodosopoulos,
- David R. Raleigh
Affiliations
- S. John Liu
- Department of Radiation Oncology, University of California San Francisco
- Tim Casey-Clyde
- Department of Radiation Oncology, University of California San Francisco
- Nam Woo Cho
- Department of Radiation Oncology, University of California San Francisco
- Jason Swinderman
- Arc Institute
- Melike Pekmezci
- Department of Pathology, University of California San Francisco
- Mark C. Dougherty
- Departments of Otolaryngology and Neurosurgery, University of Iowa
- Kyla Foster
- Department of Radiation Oncology, University of California San Francisco
- William C. Chen
- Department of Radiation Oncology, University of California San Francisco
- Javier E. Villanueva-Meyer
- Department of Radiology and Biomedical Imaging, University of California San Francisco
- Danielle L. Swaney
- J. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San Francisco
- Harish N. Vasudevan
- Department of Radiation Oncology, University of California San Francisco
- Abrar Choudhury
- Department of Radiation Oncology, University of California San Francisco
- Joanna Pak
- Department of Radiation Oncology, University of California San Francisco
- Jonathan D. Breshears
- Department of Neurological Surgery, University of California San Francisco
- Ursula E. Lang
- Department of Pathology, University of California San Francisco
- Charlotte D. Eaton
- Department of Radiation Oncology, University of California San Francisco
- Kamir J. Hiam-Galvez
- Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, and Departments of Otolaryngology, and Microbiology and Immunology, University of California San Francisco
- Erica Stevenson
- J. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San Francisco
- Kuei-Ho Chen
- J. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San Francisco
- Brian V. Lien
- Department of Neurological Surgery, University of California San Francisco
- David Wu
- Department of Neurological Surgery, University of California San Francisco
- Steve E. Braunstein
- Department of Radiation Oncology, University of California San Francisco
- Penny K. Sneed
- Department of Radiation Oncology, University of California San Francisco
- Stephen T. Magill
- Department of Neurological Surgery, Northwestern University
- Daniel Lim
- Department of Neurological Surgery, University of California San Francisco
- Michael W. McDermott
- Baptist Health Miami Neuroscience Institute
- Mitchel S. Berger
- Department of Neurological Surgery, University of California San Francisco
- Arie Perry
- Department of Neurological Surgery, University of California San Francisco
- Nevan J. Krogan
- J. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San Francisco
- Marlan R. Hansen
- Departments of Otolaryngology and Neurosurgery, University of Iowa
- Matthew H. Spitzer
- Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, and Departments of Otolaryngology, and Microbiology and Immunology, University of California San Francisco
- Luke Gilbert
- Arc Institute
- Philip V. Theodosopoulos
- Department of Neurological Surgery, University of California San Francisco
- David R. Raleigh
- Department of Radiation Oncology, University of California San Francisco
- DOI
- https://doi.org/10.1038/s41467-023-40408-5
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 19
Abstract
Abstract Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, the most common tumors of the peripheral nervous system. We find schwannomas are comprised of 2 molecular groups that are distinguished by activation of neural crest or nerve injury pathways that specify tumor cell states and the architecture of the tumor immune microenvironment. Moreover, we find radiotherapy is sufficient for interconversion of neural crest schwannomas to immune-enriched schwannomas through epigenetic and metabolic reprogramming. To define mechanisms underlying schwannoma groups, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of tumor evolution and establish a paradigm of epigenetic and metabolic reprograming of cancer cells that shapes the immune microenvironment in response to radiotherapy.
