Single-cell RNA sequencing reveals the impact of chromosomal instability on glioblastoma cancer stem cells
Authors: Zhao, Yanding and Carter, Robert and Natarajan, Sivaraman and Varn, Frederick S. and Compton, Duane A. and Gawad, Charles and Cheng, Chao and Godek, Kristina M. Year: 2019 Journal: BMC Medical Genomics
Abstract
Intra-tumor heterogeneity stems from genetic, epigenetic, functional, and environmental differences among tumor cells. A major source of genetic heterogeneity comes from DNA sequence differences and/or whole chromosome and focal copy number variations (CNVs). Whole chromosome CNVs are caused by chromosomal instability (CIN) that is defined by a persistently high rate of chromosome mis-segregation. Accordingly, CIN causes constantly changing karyotypes that result in extensive cell-to-cell genetic heterogeneity. How the genetic heterogeneity caused by CIN influences gene expression in individual cells remains unknown.
Notes
Extracted Concepts
- Copy number alterations account for most differential gene expression between NSCs and glioblastoma CSCs
- Copy number-independent gene expression differences exist in glioblastoma CSCs
- Copy number-independent gene signature correlates with tumor grade and patient survival
- Gene expression levels can computationally infer large-scale copy number variations in chromosomally unstable cells
- Gene expression scales proportionally to whole chromosome copy number in chromosomally unstable CSCs
- Neural stem cells and glioblastoma CSCs have distinct transcriptome profiles