Single-cell RNA-seq analysis of 430 cells from five primary glioblastomas revealed that these tumors are inherently variable in their expression of diverse transcriptional programs related to oncogenic signaling. This transcriptional heterogeneity reflects the complex nature of tumor cells within individual patients and indicates that simple models do not adequately capture the true diversity of gene expression patterns driving cancer progression. [@patel_single-cell_2014]
Definitions
- primary glioblastoma
- oncogenic signaling
- transcriptional programs
- gene expression
- intratumoral heterogeneity
- Single-cell RNA-seq
- tumors
- tumor cells
- models
Synthesis
Primary glioblastomas exhibit substantial intratumoral heterogeneity in the expression of oncogenic signaling pathways and transcriptional programs, as revealed through single-cell RNA sequencing analyses. This inherent variability manifests across multiple functional domains, including hypoxia-response gene expression, proliferation programs, and immune response signatures, indicating that individual tumor cells within the same glioblastoma experience or respond differently to their microenvironment. The mechanistic basis for this heterogeneity appears linked to copy number alterations and genomic instability, with gene expression patterns serving as both a readout of chromosomal architecture and a driver of phenotypic diversity among cancer stem cells that are transcriptionally distinct from normal neural stem cells. While the existence of this variability is well-established across studies, the specific molecular mechanisms that generate and maintain such heterogeneous oncogenic signaling states within individual tumors remain incompletely resolved.
Related
- Hypoxia-related transcriptional programs are variably expressed in glioblastoma cells
- Neural stem cells and glioblastoma CSCs have distinct transcriptome profiles
- Proliferation and immune response programs vary across individual glioblastoma cells