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; David R. Raleigh

doi:10.1038/s41467-023-40408-5

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. LienDavid 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^*

^*Corresponding author for this work

Neurological Surgery

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English (US)
Article number	476
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-40408-5
State	Published - Dec 2024

Funding

The authors thank Jeremy Reiter, Monika Sigg, Aparna Bhaduri, Aaron Tward, and Zora Arum for providing comments and reagents; Eric Chow, Derek Bogdanoff, Tomasz Nowakowski, Chang Kim, and Galina Schmunk for technical sequencing assistance and analysis; and Ken Probst and Noel Sirivansanti for Illustrations. This study was supported by the ASCO Conquer Cancer Sontag Foundation Young Investigator Award to SJL; NIH grants R21 HD106238 and R01 CA251221, and DOD grant NFRP NF200021 to D.R.R.; NIH grant U54 CA209891 to N.J.K.; a Children’s Tumor Foundation Young Investigator Award to H.N.V.; and an American Otological Society Fellowship Grant to M.C.D. Sequencing was performed at the UCSF CAT, supported by UCSF PBBR, RRP IMIA, and NIH grant S10 OD028511.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Liu, S. J., Casey-Clyde, T., Cho, N. W., Swinderman, J., Pekmezci, M., Dougherty, M. C., Foster, K., Chen, W. C., Villanueva-Meyer, J. E., Swaney, D. L., Vasudevan, H. N., Choudhury, A., Pak, J., Breshears, J. D., Lang, U. E., Eaton, C. D., Hiam-Galvez, K. J., Stevenson, E., Chen, K. H., ... Raleigh, D. R. (2024). Epigenetic reprogramming shapes the cellular landscape of schwannoma. Nature communications, 15(1), Article 476. https://doi.org/10.1038/s41467-023-40408-5

@article{0196caa478cc43f9abe3d63ae16479ba,

title = "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 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.",

author = "Liu, \{S. John\} and Tim Casey-Clyde and Cho, \{Nam Woo\} and Jason Swinderman and Melike Pekmezci and Dougherty, \{Mark C.\} and Kyla Foster and Chen, \{William C.\} and Villanueva-Meyer, \{Javier E.\} and Swaney, \{Danielle L.\} and Vasudevan, \{Harish N.\} and Abrar Choudhury and Joanna Pak and Breshears, \{Jonathan D.\} and Lang, \{Ursula E.\} and Eaton, \{Charlotte D.\} and Hiam-Galvez, \{Kamir J.\} and Erica Stevenson and Chen, \{Kuei Ho\} and Lien, \{Brian V.\} and David Wu and Braunstein, \{Steve E.\} and Sneed, \{Penny K.\} and Magill, \{Stephen T.\} and Daniel Lim and McDermott, \{Michael W.\} and Berger, \{Mitchel S.\} and Arie Perry and Krogan, \{Nevan J.\} and Hansen, \{Marlan R.\} and Spitzer, \{Matthew H.\} and Luke Gilbert and Theodosopoulos, \{Philip V.\} and Raleigh, \{David R.\}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2024",

month = dec,

doi = "10.1038/s41467-023-40408-5",

language = "English (US)",

volume = "15",

journal = "Nature communications",

issn = "2041-1723",

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Liu, SJ, Casey-Clyde, T, Cho, NW, Swinderman, J, Pekmezci, M, Dougherty, MC, Foster, K, Chen, WC, Villanueva-Meyer, JE, Swaney, DL, Vasudevan, HN, Choudhury, A, Pak, J, Breshears, JD, Lang, UE, Eaton, CD, Hiam-Galvez, KJ, Stevenson, E, Chen, KH, Lien, BV, Wu, D, Braunstein, SE, Sneed, PK, Magill, ST, Lim, D, McDermott, MW, Berger, MS, Perry, A, Krogan, NJ, Hansen, MR, Spitzer, MH, Gilbert, L, Theodosopoulos, PV & Raleigh, DR 2024, 'Epigenetic reprogramming shapes the cellular landscape of schwannoma', Nature communications, vol. 15, no. 1, 476. https://doi.org/10.1038/s41467-023-40408-5

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T1 - Epigenetic reprogramming shapes the cellular landscape of schwannoma

AU - Liu, S. John

AU - Casey-Clyde, Tim

AU - Cho, Nam Woo

AU - Swinderman, Jason

AU - Pekmezci, Melike

AU - Dougherty, Mark C.

AU - Foster, Kyla

AU - Chen, William C.

AU - Villanueva-Meyer, Javier E.

AU - Swaney, Danielle L.

AU - Vasudevan, Harish N.

AU - Choudhury, Abrar

AU - Pak, Joanna

AU - Breshears, Jonathan D.

AU - Lang, Ursula E.

AU - Eaton, Charlotte D.

AU - Hiam-Galvez, Kamir J.

AU - Stevenson, Erica

AU - Chen, Kuei Ho

AU - Lien, Brian V.

AU - Wu, David

AU - Braunstein, Steve E.

AU - Sneed, Penny K.

AU - Magill, Stephen T.

AU - Lim, Daniel

AU - McDermott, Michael W.

AU - Berger, Mitchel S.

AU - Perry, Arie

AU - Krogan, Nevan J.

AU - Hansen, Marlan R.

AU - Spitzer, Matthew H.

AU - Gilbert, Luke

AU - Theodosopoulos, Philip V.

AU - Raleigh, David R.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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JO - Nature communications

JF - Nature communications

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ER -

Epigenetic reprogramming shapes the cellular landscape of schwannoma

Abstract

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