Epigenetic reprogramming shapes the cellular landscape of schwannoma
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40408-5 |
| _version_ | 1797349782748921856 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | S. John Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T12:36:30Z |
| format | Article |
| id | doaj.art-6c3cb10a1a664ce0a55f363c96e7591d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T12:36:30Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6c3cb10a1a664ce0a55f363c96e7591d2024-01-21T12:27:16ZengNature PortfolioNature Communications2041-17232024-01-0115111910.1038/s41467-023-40408-5Epigenetic reprogramming shapes the cellular landscape of schwannomaS. John Liu0Tim Casey-Clyde1Nam Woo Cho2Jason Swinderman3Melike Pekmezci4Mark C. Dougherty5Kyla Foster6William C. Chen7Javier E. Villanueva-Meyer8Danielle L. Swaney9Harish N. Vasudevan10Abrar Choudhury11Joanna Pak12Jonathan D. Breshears13Ursula E. Lang14Charlotte D. Eaton15Kamir J. Hiam-Galvez16Erica Stevenson17Kuei-Ho Chen18Brian V. Lien19David Wu20Steve E. Braunstein21Penny K. Sneed22Stephen T. Magill23Daniel Lim24Michael W. McDermott25Mitchel S. Berger26Arie Perry27Nevan J. Krogan28Marlan R. Hansen29Matthew H. Spitzer30Luke Gilbert31Philip V. Theodosopoulos32David R. Raleigh33Department of Radiation Oncology, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoArc InstituteDepartment of Pathology, University of California San FranciscoDepartments of Otolaryngology and Neurosurgery, University of IowaDepartment of Radiation Oncology, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoDepartment of Radiology and Biomedical Imaging, University of California San FranciscoJ. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoDepartment of Pathology, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoParker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, and Departments of Otolaryngology, and Microbiology and Immunology, University of California San FranciscoJ. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San FranciscoJ. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoDepartment of Neurological Surgery, Northwestern UniversityDepartment of Neurological Surgery, University of California San FranciscoBaptist Health Miami Neuroscience InstituteDepartment of Neurological Surgery, University of California San FranciscoDepartment of Neurological Surgery, University of California San FranciscoJ. David Gladstone Institutes, California Institute for Quantitative Biosciences, Department of Cellular and Molecular Pharmacology, University of California San FranciscoDepartments of Otolaryngology and Neurosurgery, University of IowaParker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, and Departments of Otolaryngology, and Microbiology and Immunology, University of California San FranciscoArc InstituteDepartment of Neurological Surgery, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoAbstract 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.https://doi.org/10.1038/s41467-023-40408-5 |
| spellingShingle | 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 Epigenetic reprogramming shapes the cellular landscape of schwannoma Nature Communications |
| title | Epigenetic reprogramming shapes the cellular landscape of schwannoma |
| title_full | Epigenetic reprogramming shapes the cellular landscape of schwannoma |
| title_fullStr | Epigenetic reprogramming shapes the cellular landscape of schwannoma |
| title_full_unstemmed | Epigenetic reprogramming shapes the cellular landscape of schwannoma |
| title_short | Epigenetic reprogramming shapes the cellular landscape of schwannoma |
| title_sort | epigenetic reprogramming shapes the cellular landscape of schwannoma |
| url | https://doi.org/10.1038/s41467-023-40408-5 |
| work_keys_str_mv | AT sjohnliu epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT timcaseyclyde epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT namwoocho epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT jasonswinderman epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT melikepekmezci epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT markcdougherty epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT kylafoster epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT williamcchen epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT javierevillanuevameyer epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT daniellelswaney epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT harishnvasudevan epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT abrarchoudhury epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT joannapak epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT jonathandbreshears epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT ursulaelang epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT charlottedeaton epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT kamirjhiamgalvez epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT ericastevenson epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT kueihochen epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT brianvlien epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT davidwu epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT steveebraunstein epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT pennyksneed epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT stephentmagill epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT daniellim epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT michaelwmcdermott epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT mitchelsberger epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT arieperry epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT nevanjkrogan epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT marlanrhansen epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT matthewhspitzer epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT lukegilbert epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT philipvtheodosopoulos epigeneticreprogrammingshapesthecellularlandscapeofschwannoma AT davidrraleigh epigeneticreprogrammingshapesthecellularlandscapeofschwannoma |