Epigenetic reprogramming shapes the cellular landscape of schwannoma

作者：Siyuan Liu, Tim Casey-Clyde, Nam Woo Cho, Jason Swinderman, Melike Pekmezci, Mark C. Dougherty, Kyla Foster, William Chen, Javier Villanueva-Meyer, Danielle L. Swaney, Harish N. Vasudevan, Abrar Choudhury, Joanna Pak, Jonathan D. Breshears, Ursula E. Lang, Charlotte Eaton, Kamir J. Hiam-Galvez, Erica Stevenson, Kuei‐Ho Chen, Brian V. Lien, David Wu, Steve Braunstein, Penny K. Sneed, Stephen T. Magill, Daniel A. Lim, Michael McDermott, Mitchel S. Berger, Arie Perry, Nevan J. Krogan, Marlan R. Hansen, Matthew H. Spitzer, Luke A. Gilbert, Philip V. Theodosopoulos, David R. Raleigh · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-023-40408-5 · 被引用次数：33 · 研究领域：Neurofibromatosis and Schwannoma Cases、Glioma Diagnosis and Treatment、Neuroblastoma Research and Treatments

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.