From sorting to sequencing in the molecular era: the evolution of the cancer stem cell model in medulloblastoma

• Published in: The FEBS journal Vol. 289; no. 7; pp. 1765 - 1778
• Main Author: Werbowetski‐Ogilvie, Tamra E.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2022
• Subjects: Brain; Brain cancer; Brain tumors; Cancer; cancer stem cells; Cell differentiation; Cell Movement; Cell self-renewal; Cerebellar Neoplasms - genetics; Cerebellar Neoplasms - metabolism; Cerebellar Neoplasms - pathology; Child; Drug resistance; Glioma cells; Humans; Medulloblastoma; Medulloblastoma - genetics; Medulloblastoma - metabolism; Medulloblastoma - pathology; Neoplastic Stem Cells - pathology; scRNA‐seq; sorting; Stem cells; Subpopulations; Transcriptome; Transcriptomes; Tumor cells; Tumors; xenografts; transcriptomes; scRNA-seq; cancer stem cells; xenografts; medulloblastoma; sorting
• DOI: 10.1111/febs.15817
• ISSN: 1742-464X

The cancer stem cell (CSC) model posits that tumors contain subpopulations that display defining features of normal stem cells including self‐renewal capacity and differentiation. Tumor cells exhibiting these features are now considered to be responsible for tumor propagation and drug resistance in a wide variety of cancers. Therefore, the identification of robust CSC markers and characterization of CSC‐specific molecular signatures may lead to the identification of novel therapeutics that selectively abolish this clinically relevant cell population while preserving normal tissue. Brain tumor researchers have been at the forefront of the CSC field. From initial in vitro cell sorting experiments to the sophisticated bioinformatic technologies that now exquisitely resolve primary brain tumors at a single‐cell level, recent glioma and medulloblastoma (MB) studies have integrated developmental state with genomic and transcriptome data to identify the spectrum of cell types that may drive tumor progression. This review will examine the last two decades of CSC studies in the field. Seminal discoveries, emerging controversies, and outstanding questions will be covered with a particular focus on MB, the most common malignant primary brain tumor in children. The last two decades have seen significant gains in the understanding of the extensive inter‐ and intratumoral heterogeneity observed in the most malignant brain tumors including medulloblastoma. Cancer stem cells (CSCs) are major contributors to brain tumor cellular heterogeneity. This review will examine the seminal discoveries, emerging controversies, and outstanding questions in the CSC field with a specific focus on medulloblastoma, the most common malignant primary brain tumor in children.