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| Open AccessAstroglial Kir4.1 potassium channel deficit drives neuronal hyperexcitability and behavioral defects in Fragile X syndrome mouse model
Fragile X syndrome is a neurodevelopmental disorder with altered neuronal excitability and behavior. Here, the authors show that dysfunction of astroglial Kir4.1 potassium channels drives neuronal and behavioral impairments in a fragile X mouse model.
- Danijela Bataveljic
- , Helena Pivonkova
- & Nathalie Rouach
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Article
| Open AccessReconstruction of macroglia and adult neurogenesis evolution through cross-species single-cell transcriptomic analyses
Macroglia are neural cells that have garnered less interest than neurons despite their crucial functions including neurogenesis. Here the authors use sequencing from several species to investigate the evolution of macroglia and of adult neurogenesis.
- David Morizet
- , Isabelle Foucher
- & Laure Bally-Cuif
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| Open AccessMulticore fiber optic imaging reveals that astrocyte calcium activity in the mouse cerebral cortex is modulated by internal motivational state
Astrocyte calcium increases can alter brain state, but their dynamics during different behaviors have not been fully described. Here, the authors use multicore fiber optic imaging in freely moving mice to show that astrocyte engagement in behavior is influenced by the motivational state.
- Yung-Tian A. Gau
- , Eric T. Hsu
- & Dwight E. Bergles
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| Open AccessAge-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture
Neural circuit architecture must be maintained during an animal’s lifetime. Here, the authors show that a protective mechanism combining proteostasis and biomechanics supports the integrity of glial cells to environmental stressors.
- Francesca Coraggio
- , Mahak Bhushan
- & Georgia Rapti
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Article
| Open AccessHypothalamic astrocyte NAD+ salvage pathway mediates the coupling of dietary fat overconsumption in a mouse model of obesity
The cellular levels of the critical coenzyme nicotinamide adenine dinucleotide (NAD)+ depend on its salvage pathway. Here, the authors show that the NAD+ salvage pathway in hypothalamic astrocytes is activated to promote obesity in high fat diet-fed mice.
- Jae Woo Park
- , Se Eun Park
- & Min-Seon Kim
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Article
| Open AccessCortical astrocyte N-methyl-D-aspartate receptors influence whisker barrel activity and sensory discrimination in mice
The role of astrocyte NMDA receptor signaling in cortical circuits is unclear. Here, the authors show that NMDA receptors contribute to astrocyte calcium events and support neuronal processing of sensory information that maintains sensory activity in mice.
- Noushin Ahmadpour
- , Meher Kantroo
- & Jillian L. Stobart
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Article
| Open AccessIntegrating single-cell and spatially resolved transcriptomic strategies to survey the astrocyte response to stroke in male mice
Astrocytes adopt diverse states in response to brain injuries. Here, the authors develop a platform for spatially resolved, single-cell transcriptomics and proteomics, called tDISCO (tissue-digital microfluidic isolation of single cells for -Omics) to uncover the spatial boundaries of molecularly distinct reactive astrocyte populations in stroke.
- Erica Y. Scott
- , Nickie Safarian
- & Maryam Faiz
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| Open AccessNeuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation
The glutamate transporter GLAST in astrocyte regulates synapse function by glutamate clearance. Here, the authors show that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synaptogenesis through the intercellular association with GLAST in the developing cerebellum.
- Ken-ichi Dewa
- , Nariko Arimura
- & Mikio Hoshino
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Article
| Open AccessDisruption of lysosomal proteolysis in astrocytes facilitates midbrain organoid proteostasis failure in an early-onset Parkinson’s disease model
The protein DJ1, encoded by the PARK7 gene, is causally linked to development of early-onset PD. Here the authors observed that the loss of DJ1 function in midbrain organoids led to astrocyte dysfunction, impairing protein clearance, accumulation of α-synuclein.
- Gustavo Morrone Parfitt
- , Elena Coccia
- & Tim Ahfeldt
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Article
| Open AccessMitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex
How aging affects the brain active milieu remains unknown. Here, the authors reveal atrophy and mitochondrial malfunction of astrocytes but not neurons in older human neocortex.
- Alexander Popov
- , Nadezda Brazhe
- & Alexey Semyanov
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Article
| Open AccessCell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease
Alzheimer’s disease genetic risk is enriched in glial genes. Here, the authors derive cell-type-specific polygenic risk scores and link astrocytic genes with Aβ, and microglial genes with Aβ, tau, microglial activation, and cognitive decline.
- Hyun-Sik Yang
- , Ling Teng
- & Reisa A. Sperling
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| Open AccessA toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences
Astrocytes, highly prevalent cells in the central nervous system, have been difficult to specifically target with adeno-associated viruses (AAVs). Here, the authors present a microRNA targeting cassette that de-targets other cells, increasing astrocyte specificity of AAVs to over 99%.
- Amy J. Gleichman
- , Riki Kawaguchi
- & S. Thomas Carmichael
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Article
| Open AccessEstrogen receptor beta in astrocytes modulates cognitive function in mid-age female mice
Here the authors show in female mice at mid-life that deletion of estrogen receptor β in astrocytes induced cognitive impairment, hippocampal atrophy, glial activation and synaptic loss. ERβ ligand treatment restored cognition and decreased neuropathology in these animals.
- Noriko Itoh
- , Yuichiro Itoh
- & Rhonda R. Voskuhl
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Article
| Open AccessPD-L1 positive astrocytes attenuate inflammatory functions of PD-1 positive microglia in models of autoimmune neuroinflammation
Co-inhibitory signaling controls immune mechanisms in health and disease. The authors here show that in autoimmune neuroinflammation, astrocytic PD-L1 mitigates autoimmune neuroinflammation through interaction with PD1 expressing microglia.
- Mathias Linnerbauer
- , Tobias Beyer
- & Veit Rothhammer
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| Open AccessAstrocyte reactivity and inflammation-induced depression-like behaviors are regulated by Orai1 calcium channels
Neuroinflammation is a common feature of many neurological disorders. Here, the authors show that the Orai1 calcium channel functions as a signaling hub in astrocytes to control astrocyte-driven brain inflammation and inflammation-induced depression-like behaviors in mice.
- Michaela M. Novakovic
- , Kirill S. Korshunov
- & Murali Prakriya
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Article
| Open AccessPurinergic signaling mediates neuroglial interactions to modulate sighs
Sighs are augmented breaths necessary to maintain normal breathing. Here, the authors show that sighs are generated within the preBötzinger complex by emergent network properties that involve neuroglial interactions mediated by purinergic signaling as well as intrinsic and extrinsic modulatory inputs.
- Liza J. Severs
- , Nicholas E. Bush
- & Jan-Marino Ramirez
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Article
| Open AccessAstroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation
How developing astroglia regulate postnatal axon growth is unknown. Here, the authors define an astroglial exosome surface HepaCAM contact mechanism in regulating axon growth and how its antagonization by ApoE coordinates early postnatal pyramidal neuronal development.
- Shijie Jin
- , Xuan Chen
- & Yongjie Yang
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Article
| Open AccessAAV11 enables efficient retrograde targeting of projection neurons and enhances astrocyte-directed transduction
Viral tracers play a crucial role in studying neural circuits, but current options are limited in areas like retrograde transduction and astrocytic tropism. Here, the authors demonstrate that AAV11 function as a powerful retrograde viral tracer allowing for analyzing circuit connectivity and shows superior astrocytic tropism compared to the commonly used AAV vectors.
- Zengpeng Han
- , Nengsong Luo
- & Fuqiang Xu
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Article
| Open AccessAstrocyte-oligodendrocyte interaction regulates central nervous system regeneration
The mechanisms regulating central nervous system remyelination efficiency are poorly understood. Here, the authors show that remyelination is driven by astrocytes supporting oligodendrocyte survival, regulated by the Nrf2 and cholesterol pathways.
- Irene Molina-Gonzalez
- , Rebecca K. Holloway
- & Veronique E. Miron
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| Open AccessDistinct astrocytic modulatory roles in sensory transmission during sleep, wakefulness, and arousal states in freely moving mice
The contribution of astrocytic Ca2+ signaling to the modulation of sensory transmission in different brain states remains largely unknown. Here, the authors show two types of Ca2+ signals in the mouse barrel cortex with distinct function in sensory transmission during sleep and arousal states.
- Fushun Wang
- , Wei Wang
- & Jason H. Huang
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Article
| Open AccessAstrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice
Astrocytes act as a dynamic Cl− reservoir regulating Cl− homeostasis in the CNS. Astrocytic Cl− is high and stable during sleep, it is lower during wakefulness and fluctuates in response to sensory input and motor activity. Efflux of Cl− from astrocytes supports inhibitory transmission in the CNS.
- Verena Untiet
- , Felix R. M. Beinlich
- & Maiken Nedergaard
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Article
| Open AccessPurkinje cell dopaminergic inputs to astrocytes regulate cerebellar-dependent behavior
The role of dopamine in the cerebellum remains relatively unexplored. Here, the authors report a dopamine system in the cerebellum in mice, where Purkinje cells supply dopamine and Bergmann glia express D1 receptors. Activation of D1 receptors is found to modulate Purkinje cell activity and to affect locomotor and social behaviors.
- Chang Li
- , Natalie B. Saliba
- & Wei Li
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Article
| Open AccessRescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease
Altered Ca2+ signaling is involved in the pathogenesis of Alzheimer’s disease. Here, the authors show Ca2+ hypoactivity in astrocytes at plaque deposition onset related to reduced expression of the Ca2+ sensor STIM1 and impaired synaptic plasticity that was rescued by STIM1 overexpression in astrocytes.
- Annamaria Lia
- , Gabriele Sansevero
- & Micaela Zonta
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Article
| Open AccessMultiplex translaminar imaging in the spinal cord of behaving mice
Fluorescence imaging of the spinal cord poses challenges, including depth of imaging. Here the authors describe a custom microscope and chronically implanted microprism that enables multicolor translaminar imaging of sensory and motor evoked activity in behaving mice, and show that spinal astrocytes show sensorimotor program-dependent calcium excitation.
- Pavel Shekhtmeyster
- , Erin M. Carey
- & Axel Nimmerjahn
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Article
| Open AccessSleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport
Why fluid and solute transport in perivascular spaces is enhanced upon sleep remains elusive. Here, the authors show that each sleep cycle state displays unique perivascular dynamics, which enhances predicted fluid movement and solute transport.
- Laura Bojarskaite
- , Alexandra Vallet
- & Rune Enger
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Article
| Open AccessAn astrocytic signaling loop for frequency-dependent control of dendritic integration and spatial learning
How glial cells like astrocytes shape complex brain functions remains unclear. Here, the authors identified an astrocyte-mediated excitatory signaling loop between neurons and their own dendritic signal integration that supports spatial memory.
- Kirsten Bohmbach
- , Nicola Masala
- & Christian Henneberger
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| Open AccessAstrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice
Neuronal activity increases local cerebral blood flow (CBF) to satisfy metabolic demand, yet the role of astrocytes in this phenomenon is controversial. Here, the authors show that astrocytes amplify CBF only when neuronal activity is sustained.
- Adam Institoris
- , Milène Vandal
- & Grant R. Gordon
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Article
| Open AccessEndothelial cells regulate astrocyte to neural progenitor cell trans-differentiation in a mouse model of stroke
Damaged brains try to repair themselves by producing neurons in areas where neurogenesis does not normally occur. Here, the authors show that brain endothelial cells provide microvesicle-encased signals that convert parenchymal astrocytes into neural progenitors, thus improving outcomes after stroke.
- Wenlu Li
- , Emiri T. Mandeville
- & Eng H. Lo
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| Open AccessHippocampal astrocytes modulate anxiety-like behavior
Astrocytes affect animal behaviors by regulating the tripartite synapse. Here, the authors show that hippocampal astrocytes modulate mouse anxiety-like behavior by regulating synaptic homeostasis of dentate gyrus granule cells via ATP release.
- Woo-Hyun Cho
- , Kyungchul Noh
- & Sung Joong Lee
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Article
| Open AccessMicroglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice
Microglia are professional phagocytes in the CNS. However, which cells scavenge corpses of microglia is largely neglected. Peng and colleagues found that nonprofessional phagocytes (astrocyte) phagocytose the debris of professional phagocytes (microglia).
- Tian Zhou
- , Yuxin Li
- & Bo Peng
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Article
| Open AccessSingle cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model
Single cell RNA-sequencing of the AstTau neuron-asteroid tau assembloid model reveals excitatory neuron inflammatory signatures and an astrocytic heat shock response similar to that occurring in the brains of individuals with tauopathies, which can be ameliorated with a neuroprotective HSP90 inhibitor.
- Hannah Drew Rickner
- , Lulu Jiang
- & Christine S. Cheng
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Article
| Open AccessLesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype in mice
Effects of lesion environments on transplanted neural progenitor cells (NPC) are not well characterized. Here, the authors show that NPC transplanted into CNS lesions generate cells that share transcriptional and functional features with host wound repair astroglia in mice.
- T. M. O’Shea
- , Y. Ao
- & M. V. Sofroniew
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Article
| Open AccessCa2+-modulated photoactivatable imaging reveals neuron-astrocyte glutamatergic circuitries within the nucleus accumbens
Neuron-astrocyte communication is fundamental for brain physiology, yet the heterogeneity in the functional interaction between these two elements remains poorly understood. Here we show how different neuron-astrocyte networks integrate information from distinct glutamatergic inputs.
- Irene Serra
- , Julio Esparza
- & Marta Navarrete
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| Open AccessControlled activation of cortical astrocytes modulates neuropathic pain-like behaviour
Astrocytes may contribute to synaptic remodelling in the cortex in chronic pain states. Here the authors describe modulation of astrocyte activity to drive circuit reorganization in somatosensory cortex in mice, along with peripheral nerve block, which could be a potential therapeutic approach for the treatment of chronic pain.
- Ikuko Takeda
- , Kohei Yoshihara
- & Junichi Nabekura
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Article
| Open AccessMyotonic dystrophy RNA toxicity alters morphology, adhesion and migration of mouse and human astrocytes
Myotonic dystrophy type 1 (DM1) is characterized by debilitating neurological symptoms. Dinca et al. demonstrate the pronounced impact of DM1 on the morphology and RNA metabolism of astrocytes. Their findings suggest astroglial pathology in DM1 brain dysfunction.
- Diana M. Dincã
- , Louison Lallemant
- & Mário Gomes-Pereira
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| Open AccessCO2 signaling mediates neurovascular coupling in the cerebral cortex
The mechanism of neurovascular coupling ensures that the brain energy supply is sufficient to meet demand. Here the authors show that in this mechanism CO2 plays an important role in neuronal activity-dependent regulation of local brain blood flow.
- Patrick S. Hosford
- , Jack A. Wells
- & Alexander V. Gourine
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Article
| Open AccessAstrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age
Disruption of the blood brain barrier can occur in several diseases. Here the authors show that targeted ablation of astrocytes results in a plasticity mechanism in nearby cells to maintain cerebrovascular coverage, but that this mechanism is impaired in older animals.
- William A. Mills III
- , AnnaLin M. Woo
- & Harald Sontheimer
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| Open AccessAstrocytic phagocytosis contributes to demyelination after focal cortical ischemia in mice
Ischemic stroke can cause secondary demyelination. Whether phagocytic astrocytes can contribute to such demyelination is unclear. Here, the authors show that lipocalin-2 (LCN-2) expression increased in astrocytes upon injury. LCN-2 expressing astrocytes acquire a phagocytic phenotype and contribute to secondary demyelination in a mouse model of ischemic stroke.
- Ting Wan
- , Wusheng Zhu
- & Xinfeng Liu
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Article
| Open AccessPhysiological synaptic activity and recognition memory require astroglial glutamine
The authors present a fluorescent probe that tracks glutamine in live cells. They demonstrate the capabilities of the probe by providing direct visual evidence of an activity-dependent glutamine supply from astroglial networks to presynaptic structures under physiological conditions.
- Giselle Cheung
- , Danijela Bataveljic
- & Nathalie Rouach
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Article
| Open AccessReactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology
Alzheimer’s disease is associated with changes in astrocytes. Here the authors investigated the astrocyte translatome associated with amyloid-ß and tau pathology.
- Zoeb Jiwaji
- , Sachin S. Tiwari
- & Giles E. Hardingham
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Article
| Open AccessNogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates
Astrocytes are important players in ischemic stroke. Here, the authors use single nuclei transcriptomics to characterise marmoset astrocytes following brain injury. At functional level, they show that NogoAexpressing astrocytes limit macrophage infiltration.
- Anthony G. Boghdadi
- , Joshua Spurrier
- & James A. Bourne
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Article
| Open AccessOlfactory bulb astrocytes mediate sensory circuit processing through Sox9 in the mouse brain
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.
- Kevin Ung
- , Teng-Wei Huang
- & Benjamin R. Arenkiel
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Article
| Open AccessConservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes
Astrocytes are important players in brain development, homeostasis, and disease. Here, the authors compare the transcriptional profiles of human and mouse astrocytes. They report species-specific susceptibility to oxidative stress and response to hypoxic and inflammatory conditions.
- Jiwen Li
- , Lin Pan
- & Ye Zhang
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Article
| Open AccessPhospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer’s disease
Microglia can clear amyloid plaques in Alzheimer’s disease. Here, the authors show that specific isoforms of the phospholipid forming APOE lipoproteins activate microglia in pre-clinical mouse models of Alzheimer’s disease.
- Nicholas F. Fitz
- , Kyong Nyon Nam
- & Radosveta Koldamova
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Article
| Open AccessImpaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice
Astrocytes contribute to autism spectrum disorder (ASD) pathophysiology. Here, the authors show that IP3R2 conditional KO mice show ASD-like behaviours and identify astrocyte-derived ATP as a modulator of these behaviours in mice.
- Qian Wang
- , Ying Kong
- & Tian-Ming Gao
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Article
| Open AccessBrain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling
Lipophorin receptors (LpRs) regulate structural and functional development of neurons in Drosophila. Here authors demonstrate how short isoforms of LpR1 mediates astrocyte lipid shuttling to neuron through interacting with glia lipoprotein GLaz and the role of this pathway in dendritic morphogenesis in the fly brain.
- Jun Yin
- , Emma Spillman
- & Quan Yuan
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Article
| Open AccessAxonal chemokine-like Orion induces astrocyte infiltration and engulfment during mushroom body neuronal remodeling
Astrocytes can engulf axonal debris in the developing brain. However, the mechanisms regulating astrocyte recruitment to the proper axons is unclear. Here, the authors identify Orion as a signal for astrocyte infiltration and engulfment to the mushroom bodies in the Drosophila developing brain.
- Ana Boulanger
- , Camille Thinat
- & Jean-Maurice Dura
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Article
| Open AccessLoss of Quaking RNA binding protein disrupts the expression of genes associated with astrocyte maturation in mouse brain
Quaking RNA binding protein (QKI) is known for its role in oligodendrocyte maturation. Here, the authors define the QKI targets in the mouse brain and show that loss of QKI disrupts the expression of cell maturation-associated genes in astrocytes in vivo.
- Kristina Sakers
- , Yating Liu
- & Joseph D. Dougherty
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Article
| Open AccessSingle-cell transcriptomic reveals molecular diversity and developmental heterogeneity of human stem cell-derived oligodendrocyte lineage cells
Brain myelinating oligodendrocytes are rare and difficult to isolate, which has limited data on their development. Here the authors develop a reporter for scalable purification of human pluripotent stem cell derived oligodendrocyte lineage cells, and use this to map differentiation using single cell RNA-sequencing,
- Xitiz Chamling
- , Alyssa Kallman
- & Donald J. Zack