Journal article
Epigenetic reprogramming shapes the cellular landscape of schwannoma
Nature communications, Vol.15(1), 476
01/12/2024
DOI: 10.1038/s41467-023-40408-5
PMCID: PMC10786948
PMID: 38216587
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.
Details
- Title: Subtitle
- Epigenetic reprogramming shapes the cellular landscape of schwannoma
- Creators
- S John Liu - Wisconsin Disability AssociationTim Casey-Clyde - University of California, San FranciscoNam Woo Cho - University of California, San FranciscoJason Swinderman - University of California, San FranciscoMelike Pekmezci - University of California, San FranciscoMark C Dougherty - University of IowaKyla Foster - University of California, San FranciscoWilliam C Chen - University of California, San FranciscoJavier E Villanueva-Meyer - University of California, San FranciscoDanielle L Swaney - University of California, San FranciscoHarish N Vasudevan - University of California, San FranciscoAbrar Choudhury - University of California, San FranciscoJoanna Pak - Wisconsin Disability AssociationJonathan D Breshears - University of California, San FranciscoUrsula E Lang - University of California, San FranciscoCharlotte D Eaton - University of California, San FranciscoKamir J Hiam-Galvez - University of California, San FranciscoErica Stevenson - University of California, San FranciscoKuei-Ho Chen - University of California, San FranciscoBrian V Lien - University of California, San FranciscoDavid Wu - University of California, San FranciscoSteve E Braunstein - University of California, San FranciscoPenny K Sneed - University of California, San FranciscoStephen T Magill - Northwestern UniversityDaniel Lim - University of California, San FranciscoMichael W McDermott - New England Baptist HospitalMitchel S Berger - University of California, San FranciscoArie Perry - University of California, San FranciscoNevan J Krogan - University of California, San FranciscoMarlan R Hansen - University of IowaMatthew H Spitzer - University of California, San FranciscoLuke Gilbert - University of California, San FranciscoPhilip V Theodosopoulos - University of California, San FranciscoDavid R Raleigh - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.15(1), 476
- DOI
- 10.1038/s41467-023-40408-5
- PMID
- 38216587
- PMCID
- PMC10786948
- NLM abbreviation
- Nat Commun
- eISSN
- 2041-1723
- Language
- English
- Date published
- 01/12/2024
- Academic Unit
- Molecular Physiology and Biophysics; Neurosurgery; Otolaryngology
- Record Identifier
- 9984544956202771
Metrics
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