Single-cell profiling revealed that glioblastoma cells within a single tumor express variable levels of transcriptional programs related to cell proliferationproliferation and complement/immune response. This heterogeneity in proliferation and immune-regulatory gene expression across cells indicates functionally distinct populations with different growth potential and immunological properties. [@patel_single-cell_2014]
Definitions
- cell proliferationproliferation
- complement
- immune response
- transcriptional programs
- gene expression
- intratumoral heterogeneity
- tumor
Synthesis
Single-cell RNA sequencing of primary glioblastoma tumors has established that individual cells within the same tumor exhibit highly variable expression of transcriptional programs governing both proliferation and immune response, contradicting the assumption that bulk molecular signatures reflect uniform cellular states. This intratumoral heterogeneity extends beyond proliferation to include variable expression of hypoxia-related programs, oncogenic signaling pathways, and even the established subtype classifiers traditionally used to categorize glioblastomas at the population level. The mechanistic relationship between proliferation and outcome association remains particularly problematic, as proliferation-related gene expression confounds the interpretation of gene signatures even when classical cell cycle genes are removed, suggesting that proliferative effects permeate broader transcriptional programs including those related to immune response. What remains contested is whether the variable expression of immune response programs within individual tumor cells represents genuine functional heterogeneity in immune signaling or is an artifact of proliferation-related confounding that undermines the biological relevance of these population-level molecular classifications.
Related
- Hypoxia-related transcriptional programs are variably expressed in glioblastoma cells
- Bulk sequencing masks intratumoral copy number heterogeneity
- Cell cycle gene removal fails to eliminate proliferation confounding
- Proliferation confounds gene signature outcome association
- Established glioblastoma subtype classifiers are variably expressed within tumors
- Primary glioblastomas contain inherent variability in oncogenic signaling expression
- Gene signature outcome association questionably indicates biological relevance