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Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma

Alexander, Jes ; LaPlant, Quincey C. ; Pattwell, Siobhan S. ; Szulzewsky, Frank ; Cimino, Patrick J. ; Caruso, Francesca P. ; Pugliese, Pietro ; Chen, Zhihong ; Chardon, Florence and Hill, Andrew J. , et al. (2020) In GLIA 68(12). p.2486-2502
Abstract

Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of... (More)

Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of genetically-engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment.

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Please use this url to cite or link to this publication:
@article{fbe3c84f-31a8-4204-87af-702b4b745ff3,
  abstract     = {{<p>Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of genetically-engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment.</p>}},
  author       = {{Alexander, Jes and LaPlant, Quincey C. and Pattwell, Siobhan S. and Szulzewsky, Frank and Cimino, Patrick J. and Caruso, Francesca P. and Pugliese, Pietro and Chen, Zhihong and Chardon, Florence and Hill, Andrew J. and Spurrell, Cailyn and Ahrendsen, Dakota and Pietras, Alexander and Starita, Lea M. and Hambardzumyan, Dolores and Iavarone, Antonio and Shendure, Jay and Holland, Eric C.}},
  issn         = {{0894-1491}},
  keywords     = {{glioma; glioma stem cells; myeloid cells; radiation response; radioresistance; single-cell RNA sequencing; SP analysis}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{2486--2502}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{GLIA}},
  title        = {{Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma}},
  url          = {{http://dx.doi.org/10.1002/glia.23866}},
  doi          = {{10.1002/glia.23866}},
  volume       = {{68}},
  year         = {{2020}},
}