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Multimodal single‐cell analysis reveals distinct radioresistant stem‐like and progenitor cell populations in murine glioma
Author(s) -
Alexander Jes,
LaPlant Quincey C.,
Pattwell Siobhan S.,
Szulzewsky Frank,
Cimino Patrick J.,
Caruso Francesca P.,
Pugliese Pietro,
Chen Zhihong,
Chardon Florence,
Hill Andrew J.,
Spurrell Cailyn,
Ahrendsen Dakota,
Pietras Alexander,
Starita Lea M.,
Hambardzumyan Dolores,
Iavarone Antonio,
Shendure Jay,
Holland Eric C.
Publication year - 2020
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23866
Subject(s) - radioresistance , biology , glioma , progenitor cell , cell sorting , stem cell , cancer research , cancer stem cell , tumor microenvironment , population , cell , immunology , immune system , microbiology and biotechnology , cell culture , flow cytometry , genetics , medicine , environmental health
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.