Epigenetic reprogramming shapes the cellular landscape of schwannoma

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 and David R. Raleigh ()
Additional contact information
S. John Liu: University of California San Francisco
Tim Casey-Clyde: University of California San Francisco
Nam Woo Cho: University of California San Francisco
Jason Swinderman: Arc Institute
Melike Pekmezci: University of California San Francisco
Mark C. Dougherty: University of Iowa
Kyla Foster: University of California San Francisco
William C. Chen: University of California San Francisco
Javier E. Villanueva-Meyer: University of California San Francisco
Danielle L. Swaney: University of California San Francisco
Harish N. Vasudevan: University of California San Francisco
Abrar Choudhury: University of California San Francisco
Joanna Pak: University of California San Francisco
Jonathan D. Breshears: University of California San Francisco
Ursula E. Lang: University of California San Francisco
Charlotte D. Eaton: University of California San Francisco
Kamir J. Hiam-Galvez: University of California San Francisco
Erica Stevenson: University of California San Francisco
Kuei-Ho Chen: University of California San Francisco
Brian V. Lien: University of California San Francisco
David Wu: University of California San Francisco
Steve E. Braunstein: University of California San Francisco
Penny K. Sneed: University of California San Francisco
Stephen T. Magill: Northwestern University
Daniel Lim: University of California San Francisco
Michael W. McDermott: Baptist Health Miami Neuroscience Institute
Mitchel S. Berger: University of California San Francisco
Arie Perry: University of California San Francisco
Nevan J. Krogan: University of California San Francisco
Marlan R. Hansen: University of Iowa
Matthew H. Spitzer: University of California San Francisco
Luke Gilbert: Arc Institute
Philip V. Theodosopoulos: University of California San Francisco
David R. Raleigh: University of California San Francisco

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-40408-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-40408-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-40408-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().