Epigenetic reprogramming shapes the cellular landscape of schwannoma
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Published:2024-01-12
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Liu S. JohnORCID, Casey-Clyde TimORCID, Cho Nam Woo, Swinderman Jason, Pekmezci MelikeORCID, Dougherty Mark C.ORCID, Foster KylaORCID, Chen William C., Villanueva-Meyer Javier E., Swaney Danielle L.ORCID, Vasudevan Harish N., Choudhury AbrarORCID, Pak Joanna, Breshears Jonathan D., Lang Ursula E., Eaton Charlotte D., Hiam-Galvez Kamir J., Stevenson Erica, Chen Kuei-Ho, Lien Brian V., Wu David, Braunstein Steve E., Sneed Penny K., Magill Stephen T., Lim Daniel, McDermott Michael W., Berger Mitchel S., Perry ArieORCID, Krogan Nevan J.ORCID, Hansen Marlan R., Spitzer Matthew H.ORCID, Gilbert LukeORCID, Theodosopoulos Philip V., Raleigh David R.ORCID
Abstract
AbstractMechanisms 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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