Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression

Summary: Malignant gliomas are aggressive, hard-to-treat brain tumors. Their tumor microenvironment is massively infiltrated by myeloid cells, mostly brain-resident microglia, bone marrow (BM)-derived monocytes/macrophages, and dendritic cells that support tumor progression. Single-cell omics studie...

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Main Authors: Natalia Ochocka, Pawel Segit, Kamil Wojnicki, Salwador Cyranowski, Julian Swatler, Karol Jacek, Wiesława Grajkowska, Bozena Kaminska
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124722018757
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author Natalia Ochocka
Pawel Segit
Kamil Wojnicki
Salwador Cyranowski
Julian Swatler
Karol Jacek
Wiesława Grajkowska
Bozena Kaminska
author_facet Natalia Ochocka
Pawel Segit
Kamil Wojnicki
Salwador Cyranowski
Julian Swatler
Karol Jacek
Wiesława Grajkowska
Bozena Kaminska
author_sort Natalia Ochocka
collection DOAJ
description Summary: Malignant gliomas are aggressive, hard-to-treat brain tumors. Their tumor microenvironment is massively infiltrated by myeloid cells, mostly brain-resident microglia, bone marrow (BM)-derived monocytes/macrophages, and dendritic cells that support tumor progression. Single-cell omics studies significantly dissected immune cell heterogeneity, but dynamics and specific functions of individual subpopulations were poorly recognized. We use Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) to precisely dissect myeloid cell identities and functionalities in murine GL261 gliomas. We demonstrate that the diversity of myeloid cells infiltrating gliomas is dictated by cell type and cell state. Glioma-activated microglia are the major source of cytokines attracting other immune cells, whereas BM-derived cells show the monocyte-to-macrophage transition in the glioma microenvironment. This transition is coupled with a phenotypic switch from the IFN-related to antigen-presentation and tumor-supportive gene expression. Moreover, we found sex-dependent differences in transcriptional programs and composition of myeloid cells in murine and human glioblastomas.
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spelling doaj.art-97f3576075b6453a89a4fb80337392db2023-01-12T04:18:58ZengElsevierCell Reports2211-12472023-01-01421111971Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progressionNatalia Ochocka0Pawel Segit1Kamil Wojnicki2Salwador Cyranowski3Julian Swatler4Karol Jacek5Wiesława Grajkowska6Bozena Kaminska7Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland; Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-109 Warsaw, PolandLaboratory of Cytometry, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, PolandDepartment of Pathology, The Children’s Memorial Health Institute, 04-736 Warsaw, PolandLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland; Corresponding authorSummary: Malignant gliomas are aggressive, hard-to-treat brain tumors. Their tumor microenvironment is massively infiltrated by myeloid cells, mostly brain-resident microglia, bone marrow (BM)-derived monocytes/macrophages, and dendritic cells that support tumor progression. Single-cell omics studies significantly dissected immune cell heterogeneity, but dynamics and specific functions of individual subpopulations were poorly recognized. We use Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) to precisely dissect myeloid cell identities and functionalities in murine GL261 gliomas. We demonstrate that the diversity of myeloid cells infiltrating gliomas is dictated by cell type and cell state. Glioma-activated microglia are the major source of cytokines attracting other immune cells, whereas BM-derived cells show the monocyte-to-macrophage transition in the glioma microenvironment. This transition is coupled with a phenotypic switch from the IFN-related to antigen-presentation and tumor-supportive gene expression. Moreover, we found sex-dependent differences in transcriptional programs and composition of myeloid cells in murine and human glioblastomas.http://www.sciencedirect.com/science/article/pii/S2211124722018757CP: CancerCP: Immunology
spellingShingle Natalia Ochocka
Pawel Segit
Kamil Wojnicki
Salwador Cyranowski
Julian Swatler
Karol Jacek
Wiesława Grajkowska
Bozena Kaminska
Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression
Cell Reports
CP: Cancer
CP: Immunology
title Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression
title_full Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression
title_fullStr Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression
title_full_unstemmed Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression
title_short Specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression
title_sort specialized functions and sexual dimorphism explain the functional diversity of the myeloid populations during glioma progression
topic CP: Cancer
CP: Immunology
url http://www.sciencedirect.com/science/article/pii/S2211124722018757
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