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| Open AccessNeuronal hyperexcitability drives central and peripheral nervous system tumor progression in models of neurofibromatosis-1
Neuronal activity is emerging as a driver of nervous system tumors. Here, the authors show in mouse models of Neurofibromatosis-1 (NF1) that Nf1 mutations differentially drive both central and peripheral nervous system tumor growth in mice through reduced hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function.
- Corina Anastasaki
- , Juan Mo
- & David H. Gutmann
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Article
| Open AccessInterrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages
The intratumoural heterogeneity of spinal ependymomas and the role of microglia in tumour progression remain underexplored. Here, the authors perform single-cell RNA- and ATAC-sequencing data analysis of three subtypes and reveal tumour-associated macrophage subsets with distinct functional phenotypes.
- Qianqian Zhang
- , Sijin Cheng
- & Xiaoqun Wang
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Article
| Open AccessSchwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8
Schwann cells (SCs) can acquire a repair phenotype following nerve injury. Here, the authors show that stromal SCs in ganglioneuromas express nerve-repair genes. Importantly, neuroblastoma cells respond to repair-related SCs increasing neuronal differentiation and reducing proliferation via EGFL8.
- Tamara Weiss
- , Sabine Taschner-Mandl
- & Inge M. Ambros
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Article
| Open Access3D extracellular matrix microenvironment in bioengineered tissue models of primary pediatric and adult brain tumors
The brain extracellular matrix (ECM) is altered in brain tumors, but its role in cancer progression and drug sensitivity are difficult to study. Here the authors develop a 3D bioengineered brain tissue model using patient-derived samples and tunable brain-derived ECM to examine the interplay between cells and the ECM.
- Disha Sood
- , Min Tang-Schomer
- & David L. Kaplan
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Article
| Open AccessA STAT3-based gene signature stratifies glioma patients for targeted therapy
STAT3 activates distinct transcriptional programmes within cancer cells. In this study, the authors find that, in glioma, a STAT3-mediated expression signature can stratify patients for targeted precision therapy.
- Melanie Si Yan Tan
- , Edwin Sandanaraj
- & Carol Tang
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Article
| Open AccessNotch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma
Group 3 medulloblastoma is an aggressive pediatric brain tumour that disseminates through the leptomeningeal cerebral spinal fluid. Here, the authors show that in Group 3 medulloblastoma NOTCH1 activates BMI1 through the activation of TWIST1, driving metastasis and self-renewal, and in mouse models a NOTCH1 blocking antibody decreased spinal metastases.
- Suzana A. Kahn
- , Xin Wang
- & Samuel H. Cheshier
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Article
| Open AccessTemporal stability and molecular persistence of the bone marrow plasma cell antibody repertoire
Longevity of antibody responses has been attributed to persistence of plasma cells in mice. Here the authors provide human data in support of this model by immunoglobulin sequencing bone marrow sections from two human donors over 6.5 years to show temporal stability of plasma cell clonotypes, but not other B cells.
- Gabriel C. Wu
- , Nai-Kong V. Cheung
- & Gregory C. Ippolito
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Article
| Open AccessSpatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma
Diffuse Intrinsic Pontine Gliomas are diagnosed by sampling a small portion of the tumour. Here, using multiple samples from tumours, the authors analyse the spatial and temporal distribution of driver mutations revealing that H3K27M mutations arise first in tumorigenesis followed by a specific invariable sequence of driver mutations, which are homogeneously distributed across the tumour mass.
- Hamid Nikbakht
- , Eshini Panditharatna
- & Javad Nazarian