Epigenetic reprogramming shapes the cellular landscape of schwannoma.

Autor:	Liu SJ; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA.; Arc Institute, Palo Alto, CA, 94304, USA., Casey-Clyde T; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA., Cho NW; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, and Departments of Otolaryngology, and Microbiology and Immunology, University of California San Francisco, San Francisco, CA, 94115, USA., Swinderman J; Arc Institute, Palo Alto, CA, 94304, USA.; Department of Urology, University of California San Francisco, San Francisco, CA, 94143, USA., Pekmezci M; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA., Dougherty MC; Departments of Otolaryngology and Neurosurgery, University of Iowa, Iowa City, IA, 52242, USA., Foster K; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA., Chen WC; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA., Villanueva-Meyer JE; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA., Swaney DL; J. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA., Vasudevan HN; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA., Choudhury A; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA., Pak J; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA.; Arc Institute, Palo Alto, CA, 94304, USA., Breshears JD; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA., Lang UE; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Dermatology, University of California San Francisco, San Francisco, CA, 94115, USA., Eaton CD; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA., Hiam-Galvez KJ; Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, and Departments of Otolaryngology, and Microbiology and Immunology, University of California San Francisco, San Francisco, CA, 94115, USA., Stevenson E; J. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA., Chen KH; J. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA., Lien BV; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA., Wu D; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA., Braunstein SE; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA., Sneed PK; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA., Magill ST; Department of Neurological Surgery, Northwestern University, Chicago, IL, 60611, USA., Lim D; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA., McDermott MW; Baptist Health Miami Neuroscience Institute, Miami, FL, 33176, USA., Berger MS; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA., Perry A; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA., Krogan NJ; J. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, 94158, USA., Hansen MR; Departments of Otolaryngology and Neurosurgery, University of Iowa, Iowa City, IA, 52242, USA., Spitzer MH; Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, and Departments of Otolaryngology, and Microbiology and Immunology, University of California San Francisco, San Francisco, CA, 94115, USA., Gilbert L; Arc Institute, Palo Alto, CA, 94304, USA.; Department of Urology, University of California San Francisco, San Francisco, CA, 94143, USA., Theodosopoulos PV; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA., Raleigh DR; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA. david.raleigh@ucsf.edu.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA. david.raleigh@ucsf.edu.; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA. david.raleigh@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 Jan 12; Vol. 15 (1), pp. 476. Date of Electronic Publication: 2024 Jan 12.
DOI:	10.1038/s41467-023-40408-5
Abstrakt:	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. (© 2023. The Author(s).)
Databáze:	MEDLINE
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