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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2018.00048

Revisit the candidacy of brain cell types as the cell(s) of origin for human high-grade gliomas

  • 1School of Medicine, Zhejiang University, China

High-grade glioma, particularly, glioblastoma, is the most aggressive cancer of the central nervous system (CNS) in adults. Due to its heterogeneous nature, glioblastoma almost inevitably relapses after surgical resection and radio-/chemotherapy, and is thus highly lethal and associated with a dismal prognosis. Identifying the cell of origin has been considered an important aspect in understanding tumor heterogeneity, thereby holding great promise in designing novel therapeutic strategies for glioblastoma. Taking advantage of genetic lineage-tracing techniques, performed mainly on genetically engineered mouse models (GEMMs), multiple cell types in the CNS have been suggested as potential cells of origin for glioblastoma, among which adult neural stem cells (NSCs) and oligodendrocyte precursor cells (OPCs) are the major candidates. However, it remains highly debated whether these cell types are equally capable of transforming in patients, given that in the human brain, some cell types divide so slowly, therefore may never have a chance to transform. With the recent advances in studying adult NSCs and OPCs, particularly from the perspective of comparative biology, we now realize that notable differences exist among mammalian species. These differences have critical impacts on shaping our understanding of the cell of origin of glioma in humans. In this perspective, we update the current progress in this field and clarify some misconceptions with inputs from important findings about the biology of adult NSCs and OPCs. We propose to re-evaluate the cellular origin candidacy of these cells, with an emphasis on comparative studies between animal models and humans.

Keywords: Cell of origin, high-grade glioma, Glioblastoma, oligodendrocyte precursor cells (OPC), Genetically engineered mouse models (GEMMs), Lineage tracing, adult neural stem cells (NSCs)

Received: 27 Nov 2017; Accepted: 05 Feb 2018.

Edited by:

Margaret S. Ho, ShanghaiTech University, China

Reviewed by:

Francois M. Vallette, Institut National de la Santé et de la Recherche Médicale (INSERM), France
Mirko H. Schmidt, Universitätsmedizin der Johannes Gutenberg, Universität Mainz, Germany  

Copyright: © 2018 Shao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Chong Liu, Zhejiang University, School of Medicine, 866 Yu Hang Tang Road, Hangzhou, 310058, Zhejiang Province, China,