Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy (Human fetal brain)

Charles P. Couturier, Shamini Ayyadhury, Phuong U. Le, Javad Nadaf, Jean Monlong, Gabriele Riva, Redouane Allache, Salma Baig, Xiaohua Yan, Mathieu Bourgey, Changseok Lee, Yu Chang David Wang, V. Wee Yong, Marie-Christine Guiot, Hamed Najafabadi, Bratislav Misic, Jack Antel, Guillaume Bourque, Jiannis Ragoussis, Kevin Petrecca

Study ID

couturier_et_al_2020_fetal

Total cells

22,637

Abtract
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.

Age (weeks of gestation)

13 - 21 weeks
22637 cells

Author's cell type

Excitatory neuron (EN)
9970 cells
Excitatory neuronal progenitor (ENP)
3114 cells
Interneuron (IN)
2600 cells
Radial glia (RG)
2466 cells
Inhibitory neuronal progenitor (INP)
1593 cells
Unknown radial glia - (diffRG)
1041 cells
Truncated radial glia (tRG)
599 cells
Glial progenitor cell (GPC)
501 cells
Astrocyte (astro)
394 cells
Oligo-lineage cells (OLC)
359 cells

Condition

normal
22637 cells

Developmental stage

second trimester
22637 cells

Louvain clustering

Cluster 11
4922 cells
Cluster 9
2591 cells
Cluster 4
2590 cells
Cluster 10
2313 cells
Cluster 8
2308 cells
Cluster 7
1766 cells
Cluster 6
1735 cells
Cluster 5
1727 cells
Cluster 3
1012 cells
Cluster 2
850 cells
Cluster 1
823 cells

Quantification

CellRanger
22637 cells

Sample ID

5
6181 cells
6
3828 cells
4
3794 cells
2
3598 cells
7
2535 cells
3
1726 cells
1
975 cells

Sampling technique

surgical resection
22637 cells

Sequencing platform

Chromium v2
22637 cells

Storage technique

fresh
22637 cells

Tissue

brain
22637 cells