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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...

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Autores principales: Lessi, Francesca, Franceschi, Sara, Morelli, Mariangela, Menicagli, Michele, Pasqualetti, Francesco, Santonocito, Orazio, Gambacciani, Carlo, Pieri, Francesco, Aquila, Filippo, Aretini, Paolo, Mazzanti, Chiara Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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