Wasl is crucial to maintain microglial core activities during glioblastoma initiation stages

Mazzolini, Julie; Clerc, Sigrid Le; Morisse, Gregoire; Coulonges, Cédric; Zagury, Jean‐François; Sieger, Dirk

doi:10.1002/glia.24154

Cited by 7 publications

(5 citation statements)

References 132 publications

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“…The Wasl can be found in all subsets of myeloid cells in the brain, albeit at different levels of expression, and it is crucial for regulating microglial morphology, phagocytosis, and migration [ 69 ]. The Notch signaling pathway includes BOAT1 and ATXN1.…”

Section: Discussionmentioning

confidence: 99%

MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs

et al. 2023

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Anxiety-related disorders (ARDs) are chronic neuropsychological diseases and the sixth leading cause of disability in the world. As dysregulation of microRNAs (miRs) are observed in the pathological course of neuropsychiatric disorders, the present study aimed to introduce miRs that underlie anxiety processing in the brain. First, we collected the experimentally confirmed anxiety-related miRNAs (ARmiRs), predicted their target transcripts, and introduced critical cellular pathways with key commune hub genes. As a result, we have found nine anxiolytic and ten anxiogenic ARmiRs. The anxiolytic miRs frequently target the mRNA of Acyl-CoA synthetase long-chain family member 4 (Acsl4), AFF4-AF4/FMR2 family member 4 (Aff4), and Krüppel like transcription factor 4 (Klf4) genes, where miR-34b-5p and miR-34c-5p interact with all of them. Moreover, the anxiogenic miRs frequently target the mRNA of nine genes; among them, only two miR (miR-142-5p and miR-218-5p) have no interaction with the mRNA of trinucleotide repeat-containing adaptor 6B (Tnrc6b), and miR-124-3p interacts with all of them where MAPK is the main signaling pathway affected by both anxiolytic and anxiogenic miR. In addition, the anxiolytic miR commonly target E2F transcription factor 5 (E2F5) in the TGF-β signaling pathway, and the anxiogenic miR commonly target Ataxin 1 (Atxn1), WASP-like actin nucleation promoting factor (Wasl), and Solute Carrier Family 17 Member 6 (Slc17a6) genes in the notch signaling, adherence junction, and synaptic vesicle cycle pathways, respectively. Taken together, we conclude that the most important anxiolytic (miR-34c, Let-7d, and miR-17) and anxiogenic (miR-19b, miR-92a, and 218) miR, as hub epigenetic modulators, potentially influence the pathophysiology of anxiety, primarily via interaction with the MAPK signaling pathway. Moreover, the role of E2F5 as a novel putative target for anxiolytic miRNAs in ARDs disorders deserves further exploration.

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Section: Discussionmentioning

confidence: 99%

MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs

et al. 2023

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“…They have proven highly suited for xenotransplantation of human tumor cells, and GBM tumor cells in particular, due to high similarity with the human brain structure (Reimunde et al, 2021). Zebrafish xenograft models are used extensively to study GBM initiation, progression, migration, vasculature and invasion (Pudelko et al, 2018;Pan et al, 2020;Vittori et al, 2016;Umans et al, 2021;Mazzolini et al, 2022). Hamilton et al studied the interaction between microglia and transplanted GBM cell lines U87 and U251.…”

Section: Discussionmentioning

confidence: 99%

Single-cell profiling and zebrafish avatars revealLGALS1as immunomodulating target in glioblastoma

Finotto

Cole

Giese

et al. 2023

Preprint

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Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs - features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets.

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“…They have proven highly suited for xenotransplantation of human tumor cells, and GBM tumor cells in particular, due to high similarity with the human brain structure (Reimunde et al , 2021 ). Zebrafish xenograft models are used extensively to study GBM initiation, progression, migration, vasculature and invasion (Vittori et al , 2016 ; Pudelko et al , 2018 ; Pan et al , 2020 ; Umans et al , 2021 ; Mazzolini et al , 2022 ). Hamilton et al ( 2016 ) studied the interaction between microglia and transplanted GBM cell lines U87 and U251.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma

Finotto,

Cole,

Giese

et al. 2023

EMBO Mol Med

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Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM‐associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient‐derived GBM stem cell cultures and combined single‐cell RNA sequencing of GAM‐GBM co‐cultures and real‐time in vivo monitoring of GAM‐GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM‐induced GAM polarization and the ability to attract and activate GAMs—features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock‐out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM‐GBM interactions can be studied in a clinically relevant way using co‐cultures and avatar models, while offering new opportunities to identify promising immune‐modulating targets.

show abstract

Wasl is crucial to maintain microglial core activities during glioblastoma initiation stages

Cited by 7 publications

References 132 publications

MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs

MAPK Is a Mutual Pathway Targeted by Anxiety-Related miRNAs, and E2F5 Is a Putative Target for Anxiolytic miRNAs

Single-cell profiling and zebrafish avatars revealLGALS1as immunomodulating target in glioblastoma

Single‐cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma

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