Single-cell RNA sequencing reveals changes in glioma-associated macrophage polarization and cellular states of malignant gliomas with high AQP4 expression

Wang, Ran; Lü, Peng; Xiao, Yong; Zhou, Qi; Wang, Zhen; Tang, Lei; Xiao, Hong; Li, Li; Liu, Hongyi; Yang, Kun

doi:10.1038/s41417-022-00582-y

Cited by 8 publications

(8 citation statements)

References 65 publications

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“…The AQP4_Astro cluster may represent some common features between EPN and BG. Evidence has demonstrated that AQP4, which is usually highly expressed in brain tissues, promotes the tendency of tumor-associated macrophages to become M1 macrophages, thereby causing alterations in the cellular state of gliomas [ 37 , 38 ]. Increased expression of AQP4 leads to a reduced OS in malignant gliomas, resulting in a poor prognosis [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing of anaplastic ependymoma and H3K27M-mutant diffuse midline glioma

Zang,

Dong,

Liu

et al. 2024

BMC Neurol

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Background Anaplastic ependymoma and H3K27M-mutant diffuse midline glioma are two common subtypes of brain tumors with poor long-term prognosis. The present study analyzed and compared the differences in cell types between two tumors by single-cell RNA sequencing (scRNA-seq) technology. Methods ScRNA-seq was performed to profile cells from cancer tissue from anaplastic ependymoma patient and H3K27M-mutant diffuse midline glioma patient. Cell clustering, marker gene identification, cell type annotation, copy number variation analysis and function analysis of differentially expressed genes were then performed. Results A total of 11,219 cells were obtained from anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and these cells categorized into 12 distinct clusters. Each cell cluster could be characterized with specific cell markers to indicate cellular heterogeneity. Five cell types were annotated in each sample, including astrocyte, oligodendrocytes, microglial cell, neural progenitor cell and immune cell. The cluster types and proportion of cell types were not consistent between the two brain tumors. Functional analyses suggest that these cell clusters are involved in tumor-associated pathways, with slight differences in the cells of origin between the two tumors. In addition, cell communication analysis showed that the NRG3-ERBB4 pair is a key Ligand-receptor pair for anaplastic ependymoma, while in H3K27M-mutant diffuse midline glioma it is the PTN-PTPRZ1 pair that establishes contact with other cells. Conclusion There was intratumor heterogeneity in anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and that the subtype differences may be due to differences in the origin of the cells.

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Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing of anaplastic ependymoma and H3K27M-mutant diffuse midline glioma

Zang,

Dong,

Liu

et al. 2024

BMC Neurol

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“…Our findings begin to deconstruct complex TAM-GBM cell interactions and support ongoing therapeutic efforts aimed at repolarizing M2 macrophages towards M1-like polarization states, as well as offering novel therapeutic targets that could prevent the potent effects of M2 macrophages on GSCs. [53][54][55][56] While there have been reports of high M2 TAM accumulation in MES tumors, the mechanism behind this correlation remains unclear, although it has been proposed that MES tumors attract M2 TAMs. 8,57 Our work expands on prior studies investigating the relationship between TAM abundance and GBM subtype by proposing the possibility that M2 TAM secreted factors directly induce MES transition in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

An engineered glioblastoma model yields novel macrophage-secreted drivers of invasion

Akins,

Wilkins,

Aghi

et al. 2023

Preprint

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Glioblastomas (GBMs) are highly invasive brain tumors replete with brain- and blood-derived macrophages, collectively known as tumor-associated macrophages (TAMs). Targeting TAMs has been proposed as a therapeutic strategy but has thus far yielded limited clinical success in slowing GBM progression, due in part to an incomplete understanding of TAM function in GBM. Here, by using an engineered hyaluronic acid-based 3D invasion platform, patient-derived GBM cells, and multi-omics analysis of GBM tumor microenvironments, we show that M2-polarized macrophages stimulate GBM stem cell (GSC) mesenchymal transition and invasion. We identify TAM-derived transforming growth factor beta induced (TGFβI/BIGH3) as a pro-tumorigenic factor in the GBM microenvironment. In GBM patients, BIGH3 mRNA expression correlates with poor patient prognosis and is highest in the most aggressive GBM molecular subtype. Inhibiting TAM-derived BIGH3 signaling with a blocking antibody or small molecule inhibitor suppresses GSC invasion. Our work highlights the utility of 3Din vitrotumor microenvironment platforms to investigate TAM-cancer cell crosstalk and offers new insights into TAM function to guide novel TAM-targeting therapies.

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“…Data for the study were collected from the TCGA database 15 ( https://www.cancer.gov/ccg/ ). We downloaded the data of glioma patients (n = 706) from TCGA ( http://portal.gdc.cancer.gov ) to analyze the RNA sequencing and patient information, and we used a transfer tool that was provided by GDC to capture the statistics 16 .…”

Section: Methodsmentioning

confidence: 99%

PSMB2 plays an oncogenic role in glioma and correlates to the immune microenvironment

He,

Zhang,

Tan

et al. 2024

Sci Rep

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There has been an upward trend in the incidence of glioma, with high recurrence and high mortality. The beta subunits of the 20S proteasome are encoded by the proteasome beta (PSMB) genes and may affect the proteasome’s function in glioma, assembly and inhibitor binding. This study attempted to reveal the function of the proliferation and invasion of glioma cells, which is affected by proteasome 20S subunit beta 2 (PSMB2). We subjected the data downloaded from the TCGA database to ROC, survival, and enrichment analyses. After establishing the stable PSMB2 knockdown glioma cell line. We detect the changes in the proliferation, invasion and migration of glioma cells by plate colony formation assay, transwell assay, wound healing assay and flow cytometry and PSMB2 expression was verified by quantitative PCR and Western blotting to identify the mRNA and protein levels. PSMB2 expression was higher in glioma tissues, and its expression positively correlated with poor prognosis and high tumor grade and after PSMB2 knockdown, the proliferation, invasion and migration of glioma cells were weakened.

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Single-cell RNA sequencing reveals changes in glioma-associated macrophage polarization and cellular states of malignant gliomas with high AQP4 expression

Cited by 8 publications

References 65 publications

Single-cell RNA sequencing of anaplastic ependymoma and H3K27M-mutant diffuse midline glioma

Single-cell RNA sequencing of anaplastic ependymoma and H3K27M-mutant diffuse midline glioma

An engineered glioblastoma model yields novel macrophage-secreted drivers of invasion

PSMB2 plays an oncogenic role in glioma and correlates to the immune microenvironment

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