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Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998055/ https://www.ncbi.nlm.nih.gov/pubmed/35406690 http://dx.doi.org/10.3390/cells11071127 |
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author | Lessi, Francesca Franceschi, Sara Morelli, Mariangela Menicagli, Michele Pasqualetti, Francesco Santonocito, Orazio Gambacciani, Carlo Pieri, Francesco Aquila, Filippo Aretini, Paolo Mazzanti, Chiara Maria |
author_facet | Lessi, Francesca Franceschi, Sara Morelli, Mariangela Menicagli, Michele Pasqualetti, Francesco Santonocito, Orazio Gambacciani, Carlo Pieri, Francesco Aquila, Filippo Aretini, Paolo Mazzanti, Chiara Maria |
author_sort | Lessi, Francesca |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8998055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89980552022-04-12 Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background Lessi, Francesca Franceschi, Sara Morelli, Mariangela Menicagli, Michele Pasqualetti, Francesco Santonocito, Orazio Gambacciani, Carlo Pieri, Francesco Aquila, Filippo Aretini, Paolo Mazzanti, Chiara Maria Cells Article 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. MDPI 2022-03-26 /pmc/articles/PMC8998055/ /pubmed/35406690 http://dx.doi.org/10.3390/cells11071127 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lessi, Francesca Franceschi, Sara Morelli, Mariangela Menicagli, Michele Pasqualetti, Francesco Santonocito, Orazio Gambacciani, Carlo Pieri, Francesco Aquila, Filippo Aretini, Paolo Mazzanti, Chiara Maria Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background |
title | Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background |
title_full | Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background |
title_fullStr | Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background |
title_full_unstemmed | Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background |
title_short | Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background |
title_sort | single-cell molecular characterization to partition the human glioblastoma tumor microenvironment genetic background |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998055/ https://www.ncbi.nlm.nih.gov/pubmed/35406690 http://dx.doi.org/10.3390/cells11071127 |
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