Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated With Glioblastoma Subtypes

In glioblastoma multiforme (GBM), brain tumor initiating cells (BTICs) with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here, we applied a stem cell biology approach and compared self-renewal, marker expression, label retention and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptome signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a new framework for the study and use of BTIC lines and provides novel precursor biology insights into GBM.