Adult Human Glioblastomas Harbor Radial Glia-like Cells

Rong Wang; Roshan Sharma; Xiaojuan Shen; Ashley M Laughney; Kosuke Funato; Philip J Clark; Monika Shpokayte; Peter Morgenstern; Monalisa Navare; Yichi Xu; Shaghayegh Harbi; Ignas Masilionis; Gouri Nanjangud; Yanhong Yang; Gabriel Duran-Rehbein; Martin Hemberg; Dana Pe'er; Viviane Tabar

doi:10.1016/j.stemcr.2020.01.007

Adult Human Glioblastomas Harbor Radial Glia-like Cells

Stem Cell Reports. 2020 Feb 11;14(2):338-350. doi: 10.1016/j.stemcr.2020.01.007. Epub 2020 Jan 30.

Authors

Rong Wang¹, Roshan Sharma², Xiaojuan Shen³, Ashley M Laughney⁴, Kosuke Funato¹, Philip J Clark⁵, Monika Shpokayte⁶, Peter Morgenstern¹, Monalisa Navare¹, Yichi Xu⁷, Shaghayegh Harbi⁸, Ignas Masilionis⁹, Gouri Nanjangud¹⁰, Yanhong Yang¹, Gabriel Duran-Rehbein¹, Martin Hemberg¹¹, Dana Pe'er⁹, Viviane Tabar¹²

Affiliations

¹ Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
² Program for Computational and Systems Biology, Sloan Kettering Institute, New York, NY 10065, USA; New York Genome Center, New York, NY 10013, USA.
³ Wellcome Sanger Institute, Hinxton, Cambridgshire CB10 1SA, UK; ShaoYang University, Shaoyang, Hunan, China.
⁴ Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY 10065, USA.
⁵ Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Neurobiology and Anatomy, Drexel University College of Medicine, PA 64742, USA.
⁶ Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Brain Science, Harvard University, Boston, MA 02138, USA.
⁷ Developmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
⁸ VasculoTox, Inc. New York, NY 10010, USA.
⁹ Program for Computational and Systems Biology, Sloan Kettering Institute, New York, NY 10065, USA.
¹⁰ Molecular Cytology Core, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
¹¹ Wellcome Sanger Institute, Hinxton, Cambridgshire CB10 1SA, UK.
¹² Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: tabarv@mskcc.org.

Abstract

Radial glia (RG) cells are the first neural stem cells to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like cells with typical RG morphology and markers. The cells exhibit the classic and unique mitotic behavior of normal RG in a cell-autonomous manner. Single-cell RNA sequencing analyses of glioblastoma cells reveal transcriptionally dynamic clusters of RG-like cells that share the profiles of normal human fetal radial glia and that reside in quiescent and cycling states. Functional assays show a role for interleukin in triggering exit from dormancy into active cycling, suggesting a role for inflammation in tumor progression. These data are consistent with the possibility of persistence of RG into adulthood and their involvement in tumor initiation or maintenance. They also provide a putative cellular basis for the persistence of normal developmental programs in adult tumors.

Keywords: brain tumor; cancer stem cells; glioblastoma; inflammation; radial glia; scRNASeq; tumor mitosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cell Line, Tumor
Genome, Human
Glioblastoma / pathology*
Humans
Inflammation / pathology
Mitosis
Neuroglia / pathology*
Signal Transduction
Transcription, Genetic

Abstract

Publication types

MeSH terms

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