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Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

Astrocytes are associated with Alzheimer’s disease pathogenesis. We found that the transcription factor Sox9 functions to enhance astrocytic phagocytosis of Aβ plaques via MEGF10, and this clearance of plaques is associated with the preservation of cognitive function in mouse models.

The nature of astrocyte diversity in the adult brain has remained poorly defined. The authors identify five astrocyte subpopulations in the brain that exhibit extensive molecular and functional diversity. They uncover correlative populations in malignant glioma, providing insight into how diverse astrocyte populations contribute to synaptogenesis, tumor pathophysiology and neurological disease.

Analysis of an invasive brain cancer reveals that networks of tumour cells are linked to small groups of ‘pacemaker’ cells in which levels of calcium ions pulse periodically, driving a signal through the network that causes tumour growth.

A study in mice shows that learning induces c-Fos expression in a subset of astrocytes in the hippocampus, and that ensembles of these learning-associated astrocytes are involved in the recall of memories.

Astrocytes can regulate neuronal activity. Here, the authors show that astrocyte-specific deletion of Sox9 results in impaired neuronal sensory processing in the mouse adult olfactory bulb.

Gliomas represent the most deadly of human brain tumours; however, little progress has been made towards their successful treatment. In this Review, Deneen and colleagues discuss how glioma tumorigenesis resembles glial development and how this may inform novel therapies.

Serotonin has a role in ependymoma tumorigenesis through modifying histones and thereby regulating key transcription factors and activating specific oncogenic transcriptional networks in brain cells.

Glioblastoma tumours expressing oncogenic PIK3CA variants secrete the glycan GPC3, which promotes the formation of neural synapses, brain synaptic hyperexcitability and gliomagenesis.

Callosal projection neurons located in the hemisphere contralateral to primary glioblastoma promote progression and widespread infiltration, and screening of axon guidance genes identified SEMA4F as a key regulator of tumourigenesis and activity-dependent progression.

Inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

The functions of newborn cells arising from the subventricular zone in response to stroke have been unclear. Here, the authors show that cells migrating from the subventricular zone after stroke promote brain repair and functional recovery in mice.

Sox10 and Nuclear Factor I-A (NFIA) are transcriptional regulators of oligodendrocyte and astrocyte generation in the mammalian brain, respectively. This study describes reciprocal antagonism between these transcription factors whereby NFIA directly antagonizes Sox10 regulation of myelin gene expression in oligodendrocytes, and Sox10 negatively regulates NFIA during astrocyte differentiation. The work also demonstrates this mutual antagonism being involved in tumorigenesis, particularly during oligodendroglioma to astrocytoma conversion.

Long-range enhancer interactions regulate gene expression, yet how they influence CNS development and disease remains unclear. Glasgow et al. identified glia-specific elements and 3D chromatin architectures regulating NFIA expression during development. They also found that deletion of these enhancers suppresses NFIA expression and tumorigenesis in an in vivo glioma model.

The precise onset, temporal progression and spatial extent of neuron-tumor crosstalk in brain with Glioblastoma (GBM) are not fully understood. Here authors, using a genetic GBM mouse model, show widespread glutamate accumulation, chronic neural activity disruption between cells and brain areas, depending on tumor expansion rate and genotype with altered tumor and neural activity dynamics when adding glypican6.

The long isoform of DNMT3A is essential for mouse postnatal development and regulates bivalent genes in the brain, likely via a PRC1-mediated mechanism.

Pugh and colleagues use single-cell RNA sequencing, CRISPR screens and functional assays to define a gradient of developmental and wound-response cell states in glioblastoma stem cells, revealing insights into glioblastoma origins and potential therapeutic targets.

ATRX inactivation frequently occurs in glioma. Here, the authors explore the role of ATRX inactivation in oncogenesis, highlighting ATRX deficiency driven epigenomic changes that influence the expression of genes crucial to the oncogenic phenotype.

Optical microscopy allows neural cells to be studied in the intact brain, but imaging deep neural tissue presents substantial challenges. Prevedel and colleagues outline the principles of three-photon microscopy, highlighting its advantages for deep tissue imaging and its applications in neuroscience.

Good–bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.