{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:08:27Z","timestamp":1793909307512,"version":"4.8.0"},"reference-count":87,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS079166"],"award-info":[{"award-number":["R01NS079166"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DA036165"],"award-info":[{"award-number":["R01DA036165"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS095747"],"award-info":[{"award-number":["R01NS095747"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DA050530"],"award-info":[{"award-number":["R01DA050530"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Astrocytes and microglia are non-neuronal cells that maintain homeostasis within the central nervous system via their capacity to regulate neuronal transmission and prune synapses. Both astrocytes and microglia can undergo morphological and transcriptomic changes in response to infection with human immunodeficiency virus (HIV). While both astrocytes and microglia can be infected with HIV, HIV viral proteins in the local environment can interact with and activate these cells. Given that both astrocytes and microglia play critical roles in maintaining neuronal function, it will be critical to have an understanding of their heterogeneity and to identify genes and mechanisms that modulate their responses to HIV. Heterogeneity may include a depletion or increase in one or more astrocyte or microglial subtypes in different regions of the brain or spine as well as the gain or loss of a specific function. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool that can be used to characterise these changes within a given population. The use of this method facilitates the identification of subtypes and changes in cellular transcriptomes that develop in response to activation and various disease processes. In this review, we will examine recent studies that have used scRNA-seq to explore astrocyte and microglial heterogeneity in neurodegenerative diseases including Alzheimer\u2019s disease and amyotrophic lateral sclerosis as well as in response to HIV infection. A careful review of these studies will expand our current understanding of cellular heterogeneity at homeostasis and in response to specific disease states.<\/jats:p>","DOI":"10.3390\/cells11132021","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T10:39:13Z","timestamp":1656153553000},"page":"2021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Single-Cell RNA-Sequencing: Astrocyte and Microglial Heterogeneity in Health and Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"Michael S.","family":"Spurgat","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Stony Brook University, 101 Nicolls Rd, Stony Brook, New York, NY 11794, USA"},{"name":"Institute for Translational Sciences, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Jun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Stony Brook University, 101 Nicolls Rd, Stony Brook, New York, NY 11794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5253","DOI":"10.1242\/dev.127.24.5253","article-title":"Isolation of Radial Glial Cells by Fluorescent-Activated Cell Sorting Reveals a Neuronal Lineage","volume":"127","author":"Malatesta","year":"2000","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/369744a0","article-title":"Glutamate-Mediated Astrocyte-Neuron Signalling","volume":"369","author":"Parpura","year":"1994","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3389\/fnmol.2017.00427","article-title":"Involvement of Astrocytes in Alzheimer\u2019s Disease from a Neuroinflammatory and Oxidative Stress Perspective","volume":"10","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1038\/s41467-020-17514-9","article-title":"Knockout of Reactive Astrocyte Activating Factors Slows Disease Progression in an ALS Mouse Model","volume":"11","author":"Guttenplan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer\u2019s Disease","volume":"217","author":"Hansen","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102186","DOI":"10.1016\/j.isci.2021.102186","article-title":"Single-Cell RNA-Seq Analysis Reveals Compartment-Specific Heterogeneity and Plasticity of Microglia","volume":"24","author":"Zheng","year":"2021","journal-title":"iScience"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nn.4493","article-title":"Identification of Diverse Astrocyte Populations and Their Malignant Analogs","volume":"20","author":"Yu","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41380-019-0609-8","article-title":"Microglial Regional Heterogeneity and Its Role in the Brain","volume":"25","author":"Tan","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1194637","article-title":"Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages","volume":"330","author":"Ginhoux","year":"2010","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nn.4547","article-title":"A New Fate Mapping System Reveals Context-Dependent Random or Clonal Expansion of Microglia","volume":"20","author":"Tay","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.immuni.2015.06.012","article-title":"Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System","volume":"43","author":"Bruttger","year":"2015","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0306-4522(92)90500-2","article-title":"Turnover of Resident Microglia in the Normal Adult Mouse Brain","volume":"48","author":"Lawson","year":"1992","journal-title":"Neuroscience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1038\/nn2015","article-title":"Microglia in the Adult Brain Arise from Ly-6ChiCCR2+ Monocytes Only under Defined Host Conditions","volume":"10","author":"Mildner","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1038\/nn2014","article-title":"V Local Self-Renewal Can Sustain CNS Microglia Maintenance and Function throughout Adult Life","volume":"10","author":"Ajami","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1126\/science.1110647","article-title":"Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo","volume":"308","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.3389\/fimmu.2021.726421","article-title":"Microglia and Perivascular Macrophages Act as Antigen Presenting Cells to Promote CD8 T Cell Infiltration of the Brain","volume":"12","author":"Goddery","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/glia.20419","article-title":"Microglia Instruct Subventricular Zone Neurogenesis","volume":"54","author":"Walton","year":"2006","journal-title":"Glia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s41593-020-0654-2","article-title":"Microglia Phagocytose Myelin Sheaths to Modify Developmental Myelination","volume":"23","author":"Hughes","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1038\/nn1805","article-title":"The P2Y12 Receptor Regulates Microglial Activation by Extracellular Nucleotides","volume":"9","author":"Haynes","year":"2006","journal-title":"Nat. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0169-328X(98)00040-0","article-title":"Microglia-Specific Localisation of a Novel Calcium Binding Protein, Iba1","volume":"57","author":"Ito","year":"1998","journal-title":"Mol. Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s11481-012-9352-5","article-title":"The Role of Gap Junction Channels during Physiologic and Pathologic Conditions of the Human Central Nervous System","volume":"7","author":"Eugenin","year":"2012","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"E1738","DOI":"10.1073\/pnas.1525528113","article-title":"New Tools for Studying Microglia in the Mouse and Human CNS","volume":"113","author":"Bennett","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nn.3599","article-title":"Identification of a Unique TGF-\u03b2-Dependent Molecular and Functional Signature in Microglia","volume":"17","author":"Butovsky","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fncel.2020.00198","article-title":"Overview of General and Discriminating Markers of Differential Microglia Phenotypes","volume":"14","author":"Jurga","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nn.4222","article-title":"Microglial Brain Region-dependent Diversity and Selective Regional Sensitivities to Aging","volume":"19","author":"Grabert","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuron.2018.12.006","article-title":"Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing","volume":"101","author":"Li","year":"2019","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11706","DOI":"10.1523\/JNEUROSCI.0730-12.2012","article-title":"Lipopolysaccharide-Induced Microglial Activation and Neuroprotection against Experimental Brain Injury Is Independent of Hematogenous TLR4","volume":"32","author":"Chen","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6514","DOI":"10.1038\/ncomms7514","article-title":"TLR9 Signalling in Microglia Attenuates Seizure-Induced Aberrant Neurogenesis in the Adult Hippocampus","volume":"6","author":"Matsuda","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1186\/s12974-018-1353-8","article-title":"A Central Role for P2X7 Receptors in Human Microglia","volume":"15","author":"Janks","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"35237","DOI":"10.1074\/jbc.R114.619304","article-title":"Complexity of Danger: The Diverse Nature of Damage-Associated Molecular Patterns","volume":"289","author":"Schaefer","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/0166-2236(96)10049-7","article-title":"Microglia: A Sensor for Pathological Events in the CNS","volume":"19","author":"Kreutzberg","year":"1996","journal-title":"Trends Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/nature05713","article-title":"The Brain\u2019s Garbage Men","volume":"446","author":"Kettenmann","year":"2007","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","article-title":"Single-Cell Transcriptomic Analysis of Alzheimer\u2019s Disease","volume":"570","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A Unique Microglia Type Associated with Restricting Development of Alzheimer\u2019s Disease","volume":"169","author":"Spinrad","year":"2017","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104877","DOI":"10.1016\/j.nbd.2020.104877","article-title":"Single-Cell RNA-Seq Analysis of the Brainstem of Mutant SOD1 Mice Reveals Perturbed Cell Types and Pathways of Amyotrophic Lateral Sclerosis","volume":"141","author":"Liu","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e121718","DOI":"10.1172\/jci.insight.121718","article-title":"Single-Cell RNA Sequencing Reveals Microglia-like Cells in Cerebrospinal Fluid during Virologically Suppressed HIV","volume":"3","author":"Farhadian","year":"2018","journal-title":"JCI Insight"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer\u2019s Disease: Causes and Treatment. Molecules, 25.","DOI":"10.3390\/molecules25245789"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1084\/jem.20151948","article-title":"TREM2-Mediated Early Microglial Response Limits Diffusion and Toxicity of Amyloid Plaques","volume":"213","author":"Wang","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/j.bbadis.2016.07.007","article-title":"Transcriptional Profiling of CD11c-Positive Microglia Accumulating around Amyloid Plaques in a Mouse Model for Alzheimer\u2019s Disease","volume":"1862","author":"Kamphuis","year":"2016","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.chest.2018.06.035","article-title":"Respiratory Failure in Amyotrophic Lateral Sclerosis","volume":"155","author":"Niedermeyer","year":"2019","journal-title":"Chest"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1111\/ejn.13227","article-title":"Comparative Morphometric Analysis of Microglia in the Spinal Cord of SOD1(G93A) Transgenic Mouse Model of Amyotrophic Lateral Sclerosis","volume":"43","author":"Ohgomori","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1089\/aid.2017.0004","article-title":"Brain Microglial Cells Are Highly Susceptible to HIV-1 Infection and Spread","volume":"33","author":"Cenker","year":"2017","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.celrep.2017.07.004","article-title":"The Lifespan and Turnover of Microglia in the Human Brain","volume":"20","author":"Khosravi","year":"2017","journal-title":"Cell Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/S1473-3099(13)70269-X","article-title":"HIV-Associated Neurocognitive Disorder","volume":"13","author":"Clifford","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18719","DOI":"10.7448\/IAS.17.1.18719","article-title":"Pain in People Living with HIV\/AIDS: A Systematic Review","volume":"17","author":"Parker","year":"2014","journal-title":"J. Int. AIDS Soc."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Das Sarma, J., Burrows, A., Rayman, P., Hwang, M.-H., Kundu, S., Sharma, N., Bergmann, C., and Sen, G.C. (2020). Ifit2 Deficiency Restricts Microglial Activation and Leukocyte Migration Following Murine Coronavirus (m-CoV) CNS Infection. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1009034"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40478-020-01099-x","article-title":"Microglial Gene Signature Reveals Loss of Homeostatic Microglia Associated with Neurodegeneration of Alzheimer\u2019s Disease","volume":"9","author":"Sobue","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1073\/pnas.0500649102","article-title":"A Mouse Model for Study of Systemic HIV-1 Infection, Antiviral Immune Responses, and Neuroinvasiveness","volume":"102","author":"Potash","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/nen.0b013e31802c398d","article-title":"Pathogenesis of Simian Immunodeficiency Virus-Induced Alterations in Macaque Trigeminal Ganglia","volume":"66","author":"Laast","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s13365-017-0582-4","article-title":"An SIV\/Macaque Model Targeted to Study HIV-Associated Neurocognitive Disorders","volume":"24","author":"Beck","year":"2018","journal-title":"J. NeuroVirology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8429","DOI":"10.1523\/JNEUROSCI.5818-08.2009","article-title":"Neurobehavioral Performance in Feline Immunodeficiency Virus Infection: Integrated Analysis of Viral Burden, Neuroinflammation, and Neuronal Injury in Cortex","volume":"29","author":"Maingat","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/cne.21669","article-title":"Distinct Behaviors of Neural Stem and Progenitor Cells Underlie Cortical Neurogenesis","volume":"508","author":"Noctor","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1152\/physrev.00042.2016","article-title":"Physiology of Astroglia","volume":"98","author":"Verkhratsky","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1523\/JNEUROSCI.22-01-00183.2002","article-title":"Protoplasmic Astrocytes in CA1 Stratum Radiatum Occupy Separate Anatomical Domains","volume":"22","author":"Bushong","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S0166-2236(98)01349-6","article-title":"Tripartite Synapses: Glia, the Unacknowledged Partner","volume":"22","author":"Araque","year":"1999","journal-title":"Trends Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"44817","DOI":"10.1038\/srep44817","article-title":"Ca(2+)-Permeable AMPA Receptors in Mouse Olfactory Bulb Astrocytes","volume":"7","author":"Droste","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1002\/glia.23514","article-title":"Heterogeneity of the Astrocytic AMPA-Receptor Transcriptome","volume":"66","author":"Koch","year":"2018","journal-title":"Glia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1126\/science.1317970","article-title":"Calcium-Permeable AMPA-Kainate Receptors in Fusiform Cerebellar Glial Cells","volume":"256","author":"Burnashev","year":"1992","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0896-6273(00)80086-0","article-title":"Knockout of Glutamate Transporters Reveals a Major Role for Astroglial Transport in Excitotoxicity and Clearance of Glutamate","volume":"16","author":"Rothstein","year":"1996","journal-title":"Neuron"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.cell.2011.07.022","article-title":"Astrocytes Are Endogenous Regulators of Basal Transmission at Central Synapses","volume":"146","author":"Panatier","year":"2011","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0301-0082(00)00067-8","article-title":"Glutamate Uptake","volume":"65","author":"Danbolt","year":"2001","journal-title":"Prog. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","article-title":"The Glutamate\/GABA-Glutamine Cycle: Aspects of Transport, Neurotransmitter Homeostasis and Ammonia Transfer","volume":"98","author":"Bak","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0006-8993(79)90071-4","article-title":"Fine Structural Localization of Glutamine Synthetase in Astrocytes of Rat Brain","volume":"161","author":"Norenberg","year":"1979","journal-title":"Brain Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13115","DOI":"10.1038\/s41598-017-13243-0","article-title":"Astrocyte Calcium Waves Propagate Proximally by Gap Junction and Distally by Extracellular Diffusion of ATP Released from Volume-Regulated Anion Channels","volume":"7","author":"Fujii","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/0896-6273(92)90271-E","article-title":"Neuronal Activity Triggers Calcium Waves in Hippocampal Astrocyte Networks","volume":"8","author":"Dani","year":"1992","journal-title":"Neuron"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1126\/science.1967852","article-title":"Glutamate Induces Calcium Waves in Cultured Astrocytes: Long-Range Glial Signaling","volume":"247","author":"Finkbeiner","year":"1990","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.neuron.2014.02.007","article-title":"Gliotransmitters Travel in Time and Space","volume":"81","author":"Araque","year":"2014","journal-title":"Neuron"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0006-8993(71)90668-8","article-title":"An Acidic Protein Isolated from Fibrous Astrocytes","volume":"28","author":"Eng","year":"1971","journal-title":"Brain Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/BF00233493","article-title":"Immunocytochemical Localization of S-100 Protein in the Brain of Adult Rat. An Ultrastructural Study","volume":"214","author":"Cocchia","year":"1981","journal-title":"Cell Tissue Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/glia.20445","article-title":"S100B Expression Defines a State in Which GFAP-Expressing Cells Lose Their Neural Stem Cell Potential and Acquire a More Mature Developmental Stage","volume":"55","author":"Raponi","year":"2007","journal-title":"Glia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1523\/JNEUROSCI.4178-07.2008","article-title":"A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function","volume":"28","author":"Cahoy","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0896-6273(94)90038-8","article-title":"Localization of Neuronal and Glial Glutamate Transporters","volume":"13","author":"Rothstein","year":"1994","journal-title":"Neuron"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/glia.22990","article-title":"Gfap-Positive Radial Glial Cells Are an Essential Progenitor Population for Later-Born Neurons and Glia in the Zebrafish Spinal Cord","volume":"64","author":"Johnson","year":"2016","journal-title":"Glia"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.mcn.2005.12.006","article-title":"GFAP-Positive Progenitor Cells Produce Neurons and Oligodendrocytes throughout the CNS","volume":"31","author":"Casper","year":"2006","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1126\/science.276.5319.1699","article-title":"Epilepsy and Exacerbation of Brain Injury in Mice Lacking the Glutamate Transporter GLT-1","volume":"276","author":"Tanaka","year":"1997","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1038\/s41467-019-14198-8","article-title":"Identification of Region-Specific Astrocyte Subtypes at Single Cell Resolution","volume":"11","author":"Batiuk","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41593-021-00905-6","article-title":"Neuroinflammatory Astrocyte Subtypes in the Mouse Brain","volume":"24","author":"Hasel","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"25800","DOI":"10.1073\/pnas.2008762117","article-title":"Single-Nucleus Transcriptome Analysis Reveals Dysregulation of Angiogenic Endothelial Cells and Neuroprotective Glia in Alzheimer\u2019s Disease","volume":"117","author":"Lau","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","article-title":"V Molecular Dissection of Reactive Astrogliosis and Glial Scar Formation","volume":"32","author":"Sofroniew","year":"2009","journal-title":"Trends Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1750-3639.2003.tb00014.x","article-title":"Detection of HIV-1 DNA in Microglia\/Macrophages, Astrocytes and Neurons Isolated from Brain Tissue with HIV-1 Encephalitis by Laser Capture Microdissection","volume":"13","author":"Diamanturos","year":"2003","journal-title":"Brain Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lutgen, V., Narasipura, S.D., Barbian, H.J., Richards, M., Wallace, J., Razmpour, R., Buzhdygan, T., Ramirez, S.H., Prevedel, L., and Eugenin, E.A. (2020). HIV Infects Astrocytes in Vivo and Egresses from the Brain to the Periphery. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008381"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e01563-19","DOI":"10.1128\/JVI.01563-19","article-title":"Insights into the Gene Expression Profiles of Active and Restricted Red\/Green-HIV(+) Human Astrocytes: Implications for Shock or Lock Therapies in the Brain","volume":"94","author":"Edara","year":"2020","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1128\/JVI.06266-11","article-title":"Role of \u03b2-Catenin and TCF\/LEF Family Members in Transcriptional Activity of HIV in Astrocytes","volume":"86","author":"Narasipura","year":"2012","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1002\/glia.23310","article-title":"Astrocytes Sustain Long-Term Productive HIV-1 Infection without Establishment of Reactivable Viral Latency","volume":"66","author":"Barat","year":"2018","journal-title":"Glia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"12844","DOI":"10.1523\/JNEUROSCI.4154-07.2007","article-title":"Gap Junctions Mediate Human Immunodeficiency Virus-Bystander Killing in Astrocytes","volume":"27","author":"Eugenin","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1080\/13550280390201119","article-title":"Differential Transcriptional Regulation by Human Immunodeficiency Virus Type 1 and Gp120 in Human Astrocytes","volume":"9","author":"Galey","year":"2003","journal-title":"J. Neurovirol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/13\/2021\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:46Z","timestamp":1760139586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/13\/2021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,24]]},"references-count":87,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["cells11132021"],"URL":"https:\/\/doi.org\/10.3390\/cells11132021","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,24]]}}}