TY - JOUR
T1 - Glioblastoma scRNA-seq shows treatment-induced, immune-dependent increase in mesenchymal cancer cells and structural variants in distal neural stem cells
AU - Couturier, Charles P
AU - Nadaf, Javad
AU - Li, Zhaorong
AU - Baig, Salma
AU - Riva, Gabriele
AU - Le, Phuong
AU - Kloosterman, Daan J
AU - Monlong, Jean
AU - Nkili Meyong, Andriniaina
AU - Allache, Redouane
AU - Degenhard, Theresa
AU - Al-Rashid, Mariam
AU - Guiot, Marie-Christine
AU - Bourque, Guillaume
AU - Ragoussis, Jiannis
AU - Akkari, Leila
AU - Quintana, Francisco J
AU - Petrecca, Kevin
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2022/9/1
Y1 - 2022/9/1
N2 - BACKGROUND: Glioblastoma is a treatment-resistant brain cancer. Its hierarchical cellular nature and its tumor microenvironment (TME) before, during, and after treatments remain unresolved.METHODS: Here, we used single-cell RNA sequencing to analyze new and recurrent glioblastoma and the nearby subventricular zone (SVZ).RESULTS: We found 4 glioblastoma neural lineages are present in new and recurrent glioblastoma with an enrichment of the cancer mesenchymal lineage, immune cells, and reactive astrocytes in early recurrences. Cancer lineages were hierarchically organized around cycling oligodendrocytic and astrocytic progenitors that are transcriptomically similar but distinct to SVZ neural stem cells (NSCs). Furthermore, NSCs from the SVZ of patients with glioblastoma harbored glioblastoma chromosomal anomalies. Lastly, mesenchymal cancer cells and TME reactive astrocytes shared similar gene signatures which were induced by radiotherapy in a myeloid-dependent fashion in vivo.CONCLUSION: These data reveal the dynamic, immune-dependent nature of glioblastoma's response to treatments and identify distant NSCs as likely cells of origin.
AB - BACKGROUND: Glioblastoma is a treatment-resistant brain cancer. Its hierarchical cellular nature and its tumor microenvironment (TME) before, during, and after treatments remain unresolved.METHODS: Here, we used single-cell RNA sequencing to analyze new and recurrent glioblastoma and the nearby subventricular zone (SVZ).RESULTS: We found 4 glioblastoma neural lineages are present in new and recurrent glioblastoma with an enrichment of the cancer mesenchymal lineage, immune cells, and reactive astrocytes in early recurrences. Cancer lineages were hierarchically organized around cycling oligodendrocytic and astrocytic progenitors that are transcriptomically similar but distinct to SVZ neural stem cells (NSCs). Furthermore, NSCs from the SVZ of patients with glioblastoma harbored glioblastoma chromosomal anomalies. Lastly, mesenchymal cancer cells and TME reactive astrocytes shared similar gene signatures which were induced by radiotherapy in a myeloid-dependent fashion in vivo.CONCLUSION: These data reveal the dynamic, immune-dependent nature of glioblastoma's response to treatments and identify distant NSCs as likely cells of origin.
KW - Brain Neoplasms/pathology
KW - Glioblastoma/pathology
KW - Humans
KW - Lateral Ventricles/pathology
KW - Neural Stem Cells/pathology
KW - Single-Cell Analysis
KW - Tumor Microenvironment
U2 - 10.1093/neuonc/noac085
DO - 10.1093/neuonc/noac085
M3 - Article
C2 - 35416251
SN - 1522-8517
VL - 24
SP - 1494
EP - 1508
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - 9
ER -