Glioblastoma functional heterogeneity and enrichment of cancer stem cells with tumor recurrence Journal Article
| Authors: | Xie, X. P.; Ganbold, M.; Li, J.; Lien, M.; Chipman, M. E.; Wang, T.; Jayewickreme, C. D.; Pedraza, A. M.; Bale, T.; Tabar, V.; Brennan, C.; Sun, D.; Sharma, R.; Parada, L. F. |
| Article Title: | Glioblastoma functional heterogeneity and enrichment of cancer stem cells with tumor recurrence |
| Abstract: | Glioblastoma (GBM) is an incurable disease with high intratumoral heterogeneity. Bioinformatic studies have examined transcriptional heterogeneity with differing conclusions. Here, we characterize GBM heterogeneity and highlight critical phenotypic and hierarchical roles for quiescent cancer stem cells (qCSCs). Unsupervised single-cell transcriptomic analysis of patient-derived xenografts (PDXs) delineates six GBM transcriptional states with unique tumor exclusive gene signatures, five of which display congruence with central nervous system (CNS) cell lineages. We employ a surrogate tumor evolution assay by serial xenograft transplantation to demonstrate faithful preservation of somatic mutations, transcriptome, and qCSCs. PDX chemotherapy results in CSC resistance and expansion, also seen in recurrent patient GBM. In aggregate, these novel GBM transcriptional signatures exclusively identify tumor cells and define the hierarchical landscape as stable biologically discernible cell types that allow capture of their evolution upon recurrence, emphasizing the importance of CSCs and demonstrating general relevance to all GBM. © 2024 Elsevier Inc. |
| Keywords: | controlled study; human tissue; gene mutation; gene sequence; human cell; area under the curve; nonhuman; temozolomide; flow cytometry; nuclear magnetic resonance imaging; quality control; animal cell; mouse; cell cycle; cell infiltration; epidermal growth factor receptor; animal experiment; astrocyte; cohort analysis; genotype; recurrence; cytotoxicity; transcriptomics; carcinogenesis; tumor recurrence; glioblastoma; cancer stem cell; k ras protein; bioinformatics; fluorescence activated cell sorting; rna extraction; rna sequence; heterogeneity; tumor microenvironment; copy number variation; oligodendroglia; cancer stem cells; principal component analysis; chemoresistance; gene ontology; hierarchy; human; article; gene set enrichment analysis; patient-derived xenograft; single-cell rna sequencing; single cell rna seq; f3 receptor |
| Journal Title: | Neuron |
| Volume: | 112 |
| Issue: | 24 |
| ISSN: | 0896-6273 |
| Publisher: | Cell Press |
| Date Published: | 2024-12-18 |
| Start Page: | 4017 |
| End Page: | 4032.e6 |
| Language: | English |
| DOI: | 10.1016/j.neuron.2024.10.012 |
| PUBMED: | 39510072 |
| PROVIDER: | scopus |
| PMCID: | PMC11659040 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Luis F. Parada -- Source: Scopus |
