Single-cell molecular characterization to partition the human glioblastoma tumor microenvironment genetic background

<strong>Background: <br></strong> 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 treatme...

Full description

Bibliographic Details
Main Authors: Lessi, F, Franceschi, S, Morelli, M, Menicagli, M, Pasqualetti, F, Santonocito, O, Gambacciani, C, Pieri, F, Aquila, F, Aretini, P, Mazzanti, CM
Format: Journal article
Language:English
Published: MDPI 2022
_version_ 1797106798435500032
author Lessi, F
Franceschi, S
Morelli, M
Menicagli, M
Pasqualetti, F
Santonocito, O
Gambacciani, C
Pieri, F
Aquila, F
Aretini, P
Mazzanti, CM
author_facet Lessi, F
Franceschi, S
Morelli, M
Menicagli, M
Pasqualetti, F
Santonocito, O
Gambacciani, C
Pieri, F
Aquila, F
Aretini, P
Mazzanti, CM
author_sort Lessi, F
collection OXFORD
description <strong>Background: <br></strong> 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. <br><strong> Methods: <br></strong> 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. <br><strong> Results: <br></strong> The tumor partition in its single components allowed single-cell molecular subtyping which revealed new aspects of the GB altered genetic background. <br><strong> Conclusions: <br></strong> 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 2024-03-07T07:06:03Z
format Journal article
id oxford-uuid:4cc0215b-6e1a-4dbe-b3c6-64d015485e2e
institution University of Oxford
language English
last_indexed 2024-03-07T07:06:03Z
publishDate 2022
publisher MDPI
record_format dspace
spelling oxford-uuid:4cc0215b-6e1a-4dbe-b3c6-64d015485e2e2022-05-11T12:55:10ZSingle-cell molecular characterization to partition the human glioblastoma tumor microenvironment genetic backgroundJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4cc0215b-6e1a-4dbe-b3c6-64d015485e2eEnglishSymplectic ElementsMDPI2022Lessi, FFranceschi, SMorelli, MMenicagli, MPasqualetti, FSantonocito, OGambacciani, CPieri, FAquila, FAretini, PMazzanti, CM<strong>Background: <br></strong> 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. <br><strong> Methods: <br></strong> 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. <br><strong> Results: <br></strong> The tumor partition in its single components allowed single-cell molecular subtyping which revealed new aspects of the GB altered genetic background. <br><strong> Conclusions: <br></strong> 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.
spellingShingle Lessi, F
Franceschi, S
Morelli, M
Menicagli, M
Pasqualetti, F
Santonocito, O
Gambacciani, C
Pieri, F
Aquila, F
Aretini, P
Mazzanti, CM
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
work_keys_str_mv AT lessif singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT franceschis singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT morellim singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT menicaglim singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT pasqualettif singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT santonocitoo singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT gambaccianic singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT pierif singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT aquilaf singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT aretinip singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground
AT mazzanticm singlecellmolecularcharacterizationtopartitionthehumanglioblastomatumormicroenvironmentgeneticbackground