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      Identification of region-specific astrocyte subtypes at single cell resolution

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          Abstract

          Astrocytes, a major cell type found throughout the central nervous system, have general roles in the modulation of synapse formation and synaptic transmission, blood–brain barrier formation, and regulation of blood flow, as well as metabolic support of other brain resident cells. Crucially, emerging evidence shows specific adaptations and astrocyte-encoded functions in regions, such as the spinal cord and cerebellum. To investigate the true extent of astrocyte molecular diversity across forebrain regions, we used single-cell RNA sequencing. Our analysis identifies five transcriptomically distinct astrocyte subtypes in adult mouse cortex and hippocampus. Validation of our data in situ reveals distinct spatial positioning of defined subtypes, reflecting the distribution of morphologically and physiologically distinct astrocyte populations. Our findings are evidence for specialized astrocyte subtypes between and within brain regions. The data are available through an online database ( https://holt-sc.glialab.org/), providing a resource on which to base explorations of local astrocyte diversity and function in the brain.

          Abstract

          Astrocytes are a major cell type in the central nervous system. Using single cell transcriptome sequencing, the authors identify multiple astrocyte subtypes in the adult mouse CNS, which map to distinct spatial locations and show correlations to cell morphology and physiology.

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          Most cited references40

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          Physiology of Astroglia.

          Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense of the central nervous system (CNS). Astrocytes are highly heterogeneous in morphological appearance; they express a multitude of receptors, channels, and membrane transporters. This complement underlies their remarkable adaptive plasticity that defines the functional maintenance of the CNS in development and aging. Astrocytes are tightly integrated into neural networks and act within the context of neural tissue; astrocytes control homeostasis of the CNS at all levels of organization from molecular to the whole organ.
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            Diversity of astrocyte functions and phenotypes in neural circuits.

            Astrocytes tile the entire CNS. They are vital for neural circuit function, but have traditionally been viewed as simple, homogenous cells that serve the same essential supportive roles everywhere. Here, we summarize breakthroughs that instead indicate that astrocytes represent a population of complex and functionally diverse cells. Physiological diversity of astrocytes is apparent between different brain circuits and microcircuits, and individual astrocytes display diverse signaling in subcellular compartments. With respect to injury and disease, astrocytes undergo diverse phenotypic changes that may be protective or causative with regard to pathology in a context-dependent manner. These new insights herald the concept that astrocytes represent a diverse population of genetically tractable cells that mediate neural circuit-specific roles in health and disease.
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              Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations

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                Author and article information

                Contributors
                Matthew.Holt@kuleuven.vib.be
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                5 March 2020
                5 March 2020
                2020
                : 11
                : 1220
                Affiliations
                [1 ]Laboratory of Glia Biology, VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium
                [2 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Laboratory of Glia Biology, , KU Leuven Department of Neuroscience, ; Leuven, Belgium
                [3 ]ISNI 0000 0001 2159 175X, GRID grid.10328.38, Life and Health Sciences Research Institute (ICVS), , University of Minho, ; Braga, Portugal
                [4 ]ISNI 0000 0001 2159 175X, GRID grid.10328.38, ICVS/3Bs - PT Government Associate Laboratory, ; Braga, Portugal
                [5 ]IPCA-EST-2Ai, Polytechnic Institute of Cávado and Ave, Applied Artificial Intelligence Laboratory, IPCA Campus, Barcelos, Portugal
                [6 ]ISNI 0000 0004 0606 5382, GRID grid.10306.34, Sanger Institute–EBI Single-Cell Genomics Centre, , Wellcome Trust Sanger Institute, ; Hinxton, UK
                [7 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, KU Leuven Department of Human Genetics, ; Leuven, Belgium
                [8 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, , University of Oxford, ; Oxford, UK
                [9 ]ISNI 0000 0004 1936 7988, GRID grid.4305.2, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, , University of Edinburgh, ; Edinburgh, UK
                [10 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Leuven Brain Institute, KU Leuven, ; Leuven, Belgium
                [11 ]Present Address: The Bioinformatics CRO, Niceville, Florida 32578 USA
                Author information
                http://orcid.org/0000-0001-6681-4048
                http://orcid.org/0000-0002-3816-4583
                http://orcid.org/0000-0002-1005-2328
                http://orcid.org/0000-0003-0202-7816
                http://orcid.org/0000-0002-8958-4027
                Article
                14198
                10.1038/s41467-019-14198-8
                7058027
                32139688
                4e170e63-c047-4d0d-9e13-1520518f1ab5
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 November 2019
                : 17 December 2019
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                fluorescence in situ hybridization,rna sequencing,astrocyte,molecular neuroscience

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