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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/7/1127 |
| _version_ | 1811153705109553152 |
|---|---|
| author | Francesca Lessi Sara Franceschi Mariangela Morelli Michele Menicagli Francesco Pasqualetti Orazio Santonocito Carlo Gambacciani Francesco Pieri Filippo Aquila Paolo Aretini Chiara Maria Mazzanti |
| author_facet | Francesca Lessi Sara Franceschi Mariangela Morelli Michele Menicagli Francesco Pasqualetti Orazio Santonocito Carlo Gambacciani Francesco Pieri Filippo Aquila Paolo Aretini Chiara Maria Mazzanti |
| author_sort | Francesca Lessi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T12:00:34Z |
| format | Article |
| id | doaj.art-62bf9ab8598d43e6b700523fc6ee3dc3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T12:00:34Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-62bf9ab8598d43e6b700523fc6ee3dc32023-11-30T23:03:51ZengMDPI AGCells2073-44092022-03-01117112710.3390/cells11071127Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic BackgroundFrancesca Lessi0Sara Franceschi1Mariangela Morelli2Michele Menicagli3Francesco Pasqualetti4Orazio Santonocito5Carlo Gambacciani6Francesco Pieri7Filippo Aquila8Paolo Aretini9Chiara Maria Mazzanti10Section of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, ItalySection of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, ItalySection of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, ItalySection of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, ItalyDepartment of Radiation Oncology, Azienda Ospedaliera Universitaria Pisana, University of Pisa, 56126 Pisa, ItalyDivision of Neurosurgery, Spedali Riuniti di Livorno—USL Toscana Nord-Ovest, 57124 Livorno, ItalyDivision of Neurosurgery, Spedali Riuniti di Livorno—USL Toscana Nord-Ovest, 57124 Livorno, ItalyDivision of Neurosurgery, Spedali Riuniti di Livorno—USL Toscana Nord-Ovest, 57124 Livorno, ItalyDivision of Neurosurgery, Spedali Riuniti di Livorno—USL Toscana Nord-Ovest, 57124 Livorno, ItalySection of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, ItalySection of Genomics and Transcriptomics, Fondazione Pisana per la Scienza, San Giuliano Terme, 56017 Pisa, ItalyBackground: 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.https://www.mdpi.com/2073-4409/11/7/1127single-cellglioblastomatumor microenvironmentcopy number aberrationsDEPArray |
| spellingShingle | Francesca Lessi Sara Franceschi Mariangela Morelli Michele Menicagli Francesco Pasqualetti Orazio Santonocito Carlo Gambacciani Francesco Pieri Filippo Aquila Paolo Aretini Chiara Maria Mazzanti Single-Cell Molecular Characterization to Partition the Human Glioblastoma Tumor Microenvironment Genetic Background Cells single-cell glioblastoma tumor microenvironment copy number aberrations DEPArray |
| 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 | single-cell glioblastoma tumor microenvironment copy number aberrations DEPArray |
| url | https://www.mdpi.com/2073-4409/11/7/1127 |
| work_keys_str_mv | AT francescalessi singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT sarafranceschi singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT mariangelamorelli singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT michelemenicagli singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT francescopasqualetti singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT oraziosantonocito singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT carlogambacciani singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT francescopieri singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT filippoaquila singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT paoloaretini singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground AT chiaramariamazzanti singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground |