Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background.
DEPArray
copy number aberrations
glioblastoma
single-cell
tumor microenvironment
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
26 03 2022
26 03 2022
Historique:
received:
04
03
2022
revised:
17
03
2022
accepted:
24
03
2022
entrez:
12
4
2022
pubmed:
13
4
2022
medline:
14
4
2022
Statut:
epublish
Résumé
Glioblastoma (GB) is a devastating primary brain malignancy. The recurrence of GB is inevitable despite the standard treatment of surgery, chemotherapy, and radiation, and the median survival is limited to around 15 months. The barriers to treatment include the complex interactions among the different cellular components inhabiting the tumor microenvironment. The complex heterogeneous nature of GB cells is helped by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance. By using fluorescent multiple labeling and a DEPArray cell separator, we recovered several single cells or groups of single cells from populations of different origins from IDH-WT GB samples. From each GB sample, we collected astrocytes-like (GFAP+), microglia-like (IBA1+), stem-like cells (CD133+), and endothelial-like cells (CD105+) and performed Copy Number Aberration (CNA) analysis with a low sequencing depth. The same tumors were subjected to a bulk CNA analysis. The tumor partition in its single components allowed single-cell molecular subtyping which revealed new aspects of the GB altered genetic background. Nowadays, single-cell approaches are leading to a new understanding of GB physiology and disease. Moreover, single-cell CNAs resource will permit new insights into genome heterogeneity, mutational processes, and clonal evolution in malignant tissues.
Sections du résumé
BACKGROUND
Glioblastoma (GB) is a devastating primary brain malignancy. The recurrence of GB is inevitable despite the standard treatment of surgery, chemotherapy, and radiation, and the median survival is limited to around 15 months. The barriers to treatment include the complex interactions among the different cellular components inhabiting the tumor microenvironment. The complex heterogeneous nature of GB cells is helped by the local inflammatory tumor microenvironment, which mostly induces tumor aggressiveness and drug resistance.
METHODS
By using fluorescent multiple labeling and a DEPArray cell separator, we recovered several single cells or groups of single cells from populations of different origins from IDH-WT GB samples. From each GB sample, we collected astrocytes-like (GFAP+), microglia-like (IBA1+), stem-like cells (CD133+), and endothelial-like cells (CD105+) and performed Copy Number Aberration (CNA) analysis with a low sequencing depth. The same tumors were subjected to a bulk CNA analysis.
RESULTS
The tumor partition in its single components allowed single-cell molecular subtyping which revealed new aspects of the GB altered genetic background.
CONCLUSIONS
Nowadays, single-cell approaches are leading to a new understanding of GB physiology and disease. Moreover, single-cell CNAs resource will permit new insights into genome heterogeneity, mutational processes, and clonal evolution in malignant tissues.
Identifiants
pubmed: 35406690
pii: cells11071127
doi: 10.3390/cells11071127
pmc: PMC8998055
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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