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

Jes Alexander, Quincey C. LaPlant, Siobhan S. Pattwell, Frank Szulzewsky, Patrick J. Cimino, Francesca P. Caruso, Pietro Pugliese, Zhihong Chen, Florence Chardon, Andrew J. Hill, Cailyn Spurrell, Dakota Ahrendsen, Alexander Pietras, Lea M. Starita, Dolores Hambardzumyan, Antonio Iavarone, Jay Shendure, Eric C. Holland

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)2486-2502
Number of pages17
JournalGLIA
Volume68
Issue number12
Early online date2020 Jul 4
DOIs
Publication statusPublished - 2020 Dec

Subject classification (UKÄ)

  • Cancer and Oncology
  • Cell and Molecular Biology

Free keywords

  • glioma
  • glioma stem cells
  • myeloid cells
  • radiation response
  • radioresistance
  • single-cell RNA sequencing
  • SP analysis

Fingerprint

Dive into the research topics of 'Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma'. Together they form a unique fingerprint.

Cite this