Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
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, a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2021.703810/full |
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| author | Aaron J. Moulson Aaron J. Moulson Jordan W. Squair Robin J. M. Franklin Wolfram Tetzlaff Wolfram Tetzlaff Wolfram Tetzlaff Peggy Assinck Peggy Assinck |
| author_facet | Aaron J. Moulson Aaron J. Moulson Jordan W. Squair Robin J. M. Franklin Wolfram Tetzlaff Wolfram Tetzlaff Wolfram Tetzlaff Peggy Assinck Peggy Assinck |
| author_sort | Aaron J. Moulson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T21:54:02Z |
| format | Article |
| id | doaj.art-3159265feb344db482e6ac1b259efca0 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-14T21:54:02Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-3159265feb344db482e6ac1b259efca02022-12-21T22:46:10ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022021-07-011510.3389/fncel.2021.703810703810Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?Aaron J. Moulson0Aaron J. Moulson1Jordan W. Squair2Robin J. M. Franklin3Wolfram Tetzlaff4Wolfram Tetzlaff5Wolfram Tetzlaff6Peggy Assinck7Peggy Assinck8Faculty of Medicine, University of British Columbia, Vancouver, BC, CanadaInternational Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CanadaDepartment 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, SwitzerlandWellcome Trust - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomInternational Collaboration on Repair Discoveries (ICORD), Vancouver, BC, CanadaDepartment of Zoology, University of British Columbia, Vancouver, BC, CanadaDepartment of Surgery, University of British Columbia, Vancouver, BC, CanadaWellcome Trust - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United KingdomCentre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United KingdomAstrocytes 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.https://www.frontiersin.org/articles/10.3389/fncel.2021.703810/fullreactive astrocytesheterogeneityplasticitysingle-cell RNA sequencingischemic strokeCNS demyelination |
| spellingShingle | Aaron J. Moulson Aaron J. Moulson Jordan W. Squair Robin J. M. Franklin Wolfram Tetzlaff Wolfram Tetzlaff Wolfram Tetzlaff Peggy Assinck Peggy Assinck Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity? Frontiers in Cellular Neuroscience reactive astrocytes heterogeneity plasticity single-cell RNA sequencing ischemic stroke CNS demyelination |
| title | Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity? |
| title_full | Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity? |
| title_fullStr | Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity? |
| title_full_unstemmed | Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity? |
| title_short | Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity? |
| title_sort | diversity of reactive astrogliosis in cns pathology heterogeneity or plasticity |
| topic | reactive astrocytes heterogeneity plasticity single-cell RNA sequencing ischemic stroke CNS demyelination |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2021.703810/full |
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