TOX3 regulates neural progenitor identity

Sahu, Sanjeeb Kumar; Fritz, Alina; Tiwari, Neha; Kovacs, Zsuzsa; Pouya, Alireza; Wüllner, Verena; Bora, Pablo; Schacht, Teresa; Baumgart, Jan; Péron, Sophie; Berninger, Benedikt; Tiwari, Vijay; Methner, Axel

doi:10.1016/j.bbagrm.2016.04.005

Cited by 18 publications

(11 citation statements)

References 26 publications

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“…Among the TFs that exhibit MR activity in Cluster 17, were Sirtuin 2 ( Sirt2 ), an NAD‐dependent histone deacetylase specifically expressed in oligodendrocytes to modulate the cytoskeleton during differentiation and maturation and the NK2 Homeobox 2 ( Nkx2‐2 ) homeodomain TF, a well‐known MR of cell fate determination and differentiation in the oligodendrocyte lineage (Figure S3d) (Qi et al, 2001; Tang & Chua, 2008). The MRs activated in Cluster 23 included, TOX High Mobility Group Box Family Member 3 ( Tox3 ), a TF regulating neural progenitor identity, and Forkhead Box P2 ( Foxp2 ), a TF crucial for specialized neuronal activities (Figure S3e) (Enard, 2011; Sahu et al, 2016). Finally, the TFs acting as specific MRs of Cluster 22 include TEA Domain Transcription Factor 1 ( Tead1 ) and Smad family member 3 ( Smad3 ) (Figure 4b).…”

Section: Resultsmentioning

confidence: 99%

Multimodal single‐cell analysis reveals distinct radioresistant stem‐like and progenitor cell populations in murine glioma

Alexander

LaPlant

Pattwell

et al. 2020

Glia

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Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of genetically-engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment.

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Section: Resultsmentioning

confidence: 99%

Multimodal single‐cell analysis reveals distinct radioresistant stem‐like and progenitor cell populations in murine glioma

Alexander

LaPlant

Pattwell

et al. 2020

Glia

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“…Our work in granulosa cells showed that TOX3 exerts an antiapoptotic effect on ovarian granulosa cells. In previous studies, TOX3 has been demonstrated to be a survival factor (12) or a pro-proliferation factor (14,38) in several biological processes. TOX3 also upregulates a set of ER target genes that are involved in the cell cycle, cancer progression, and metastasis (14).…”

Section: Discussionmentioning

confidence: 99%

TOX3 Promotes Ovarian Estrogen Synthesis: An RNA-Sequencing and Network Study

et al. 2021

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BackgroundWomen who undergo chronic exposure to excessive estrogen are at a high risk of developing breast cancer. TOX3 has been reported to be highly expressed in breast tumors and is closely related to estrogen receptors. However, the effect of TOX3 on estrogen synthesis remains poorly understood.MethodsUsing lentiviruses as a vector, we stably overexpressed TOX3 in the ovarian granulosa cell line KGN, the cells where estradiol is primarily produced, to investigate its role in estrogen production as well as cell viability and apoptosis. RNA-Sequencing was applied to uncover the global gene expression upon TOX3 overexpression.ResultsWe observed an increased level of cell viability and a reduced cell apoptosis rate after TOX3 overexpression, and the level of estradiol in the cell culture supernatant also increased significantly. Gene set enrichment analysis of the transcriptome showed that the ovarian steroidogenesis pathway was significantly enriched. Similarly, pathway mapping using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses also showed that TOX3 overexpression affects the ovarian steroidogenesis pathway. Further experiments showed that upregulated FSHR, CYP19A1, and BMP6 accounted for the enhanced estrogen synthesis.ConclusionOur study demonstrated that TOX3 quantitatively and qualitatively stimulates estrogen synthesis by enhancing estrogen signaling pathway–related gene expression in ovarian granulosa cells. These findings suggest that TOX3 may play a vital role in the pathogenesis of breast cancer.

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“…The lack of volume differences supports previous findings ( 12 – 15 ), suggesting that RLS is not accompanied by any changes of subcortical gray matter. Instead, it seems more likely that alterations of the dopaminergic system ( 6 ), possibly induced by genes involved in neurodevelopment [ MEIS1 ( 35 , 36 ) and TOX3 ( 37 )], protection of dopaminergic neurons [ MAP2K5 ( 38 )], sleep disturbances [ BTBD9 ( 39 )], modulation of dopaminergic neurotransmission [ PTPRD ( 40 )], and iron regulation within the brain [ BTBD9 ( 41 )], may lead to changes in functional brain networks. In particular, increased functional connectivity has been reported in sensory-thalamic, basal ganglia-thalamic, and other cortical and subcortical networks in patients with RLS, whereas symptom severity correlated with increased network connectivity ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Lack of Association Between Shape and Volume of Subcortical Brain Structures and Restless Legs Syndrome

Hermesdorf¹,

Sundermann²,

Rawal³

et al. 2018

Front. Neurol.

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ObjectivePrevious studies on patients with restless legs syndrome (RLS) yielded inconclusive results in the magnetic resonance imaging (MRI)-based analyses of alterations of subcortical structures in the brain. The aim of this study was to compare volumes as well as shapes of subcortical structures and the hippocampus between RLS cases and controls. Additionally, the associations between the genetic risks for RLS and subcortical volumes were investigated.MethodsWe compared volumetric as well as shape differences assessed by 3 T MRI in the caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus in 39 RLS cases versus 117 controls, nested within a population-based sample. In a subsample, we explored associations between known genetic risk markers for RLS and the volumes of the subcortical structures and the hippocampus.ResultsNo significant differences between RLS cases and controls in subcortical and hippocampal shapes and volumes were observed. Furthermore, the genetic risk for RLS was unrelated to any alterations of subcortical and hippocampal gray matter volume.InterpretationWe conclude that neither RLS nor the genetic risk for the disease give rise to changes in hippocampal and subcortical shapes and gray matter volumes.

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TOX3 regulates neural progenitor identity

Cited by 18 publications

References 26 publications

Multimodal single‐cell analysis reveals distinct radioresistant stem‐like and progenitor cell populations in murine glioma

Multimodal single‐cell analysis reveals distinct radioresistant stem‐like and progenitor cell populations in murine glioma

TOX3 Promotes Ovarian Estrogen Synthesis: An RNA-Sequencing and Network Study

Lack of Association Between Shape and Volume of Subcortical Brain Structures and Restless Legs Syndrome

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