10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as “reactive astrogliosis.” Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions.

          Related collections

          Most cited references454

          • Record: found
          • Abstract: found
          • Article: not found

          Integrating single-cell transcriptomic data across different conditions, technologies, and species

          Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. However, identifying subpopulations of cells that are present across multiple data sets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq data sets based on common sources of variation, enabling the identification of shared populations across data sets and downstream comparative analysis. We apply this approach, implemented in our R toolkit Seurat (http://satijalab.org/seurat/), to align scRNA-seq data sets of peripheral blood mononuclear cells under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across data sets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq data sets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Neurotoxic reactive astrocytes are induced by activated microglia

            A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets.

              Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq, a strategy for quickly profiling thousands of individual cells by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together. Drop-seq analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts' cell of origin. We analyzed transcriptomes from 44,808 mouse retinal cells and identified 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes. Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution. VIDEO ABSTRACT.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                26 July 2021
                2021
                : 15
                : 703810
                Affiliations
                [1] 1Faculty of Medicine, University of British Columbia , Vancouver, BC, Canada
                [2] 2International Collaboration on Repair Discoveries (ICORD) , Vancouver, BC, Canada
                [3] 3Department of Clinical Neuroscience, Faculty of Life Sciences, Center for Neuroprosthetics and Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), NeuroRestore, Lausanne University Hospital (CHUV), University of Lausanne (UNIL) , Lausanne, Switzerland
                [4] 4Wellcome Trust - MRC Cambridge Stem Cell Institute, University of Cambridge , Cambridge, United Kingdom
                [5] 5Department of Zoology, University of British Columbia , Vancouver, BC, Canada
                [6] 6Department of Surgery, University of British Columbia , Vancouver, BC, Canada
                [7] 7Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh , Edinburgh, United Kingdom
                Author notes

                Edited by: Dimitrios Davalos, Case Western Reserve University, United States

                Reviewed by: Shane A. Liddelow, New York University, United States; Jessica L. Williams, Cleveland Clinic, United States

                *Correspondence: Peggy Assinck, pa465@ 123456cam.ac.uk

                These authors have contributed equally to this work and share first authorship

                This article was submitted to Non-Neuronal Cells, a section of the journal Frontiers in Cellular Neuroscience

                Article
                10.3389/fncel.2021.703810
                8349991
                34381334
                968442b5-9afa-4439-803a-877eca9966fe
                Copyright © 2021 Moulson, Squair, Franklin, Tetzlaff and Assinck.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 April 2021
                : 02 July 2021
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 457, Pages: 32, Words: 0
                Categories
                Neuroscience
                Review

                Neurosciences
                reactive astrocytes,heterogeneity,plasticity,single-cell rna sequencing,ischemic stroke,cns demyelination,traumatic brain injury (tbi),spinal cord injury (sci)

                Comments

                Comment on this article