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

AI Article Synopsis

  • Malignant gliomas are aggressive brain tumors with a complex environment heavily populated by immune cells like microglia and macrophages, which promote tumor growth.
  • Using CITE-seq technology, the authors identified various myeloid cell subpopulations in mouse gliomas and revealed their distinct roles and states.
  • They found that glioma-activated microglia produce cytokines that recruit other immune cells, while bone marrow-derived cells transition from monocytes to macrophages, showing sex-based differences in their gene expression and composition.

Article Abstract

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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Source
http://dx.doi.org/10.1016/j.celrep.2022.111971DOI Listing

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