Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy.
Charles P CouturierShamini AyyadhuryPhuong U LeJavad NadafJean MonlongGabriele RivaRedouane AllacheSalma BaigXiaohua YanMathieu BourgeyChangseok LeeYu Chang David WangVoon Wee YongMarie-Christine GuiotHamed S NajafabadiBratislav MisicJack AntelGuillaume BourqueJiannis RagoussisKevin PetreccaPublished in: Nature communications (2020)
Cancer stem cells are critical for cancer initiation, development, and treatment resistance. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA sequencing on 53586 adult glioblastoma cells and 22637 normal human fetal brain cells, and compared the lineage hierarchy of the developing human brain to the transcriptome of cancer cells. We find a conserved neural tri-lineage cancer hierarchy centered around glial progenitor-like cells. We also find that this progenitor population contains the majority of the cancer's cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.
Keyphrases
- single cell
- rna seq
- cancer stem cells
- induced apoptosis
- high throughput
- papillary thyroid
- cell cycle arrest
- endothelial cells
- endoplasmic reticulum stress
- transcription factor
- resting state
- cell death
- stem cells
- dna methylation
- gene expression
- spinal cord injury
- bone marrow
- multiple sclerosis
- spinal cord
- mesenchymal stem cells
- smoking cessation