Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain

By A. Buffo, Inmaculada Rite, P. Tripathi, A. Lepier, D. Çolak, A. Horn, Tetsuji Mori, M. Götz. Proceedings of the National Academy of Sciences of the United States of America, 2008

792 citations recorded by the source corpus.

Reactive gliosis is the universal reaction to brain injury, but the precise origin and subsequent fate of the glial cells reacting to injury are unknown. Astrocytes react to injury by hypertrophy and up-regulation of the glial-fibrillary acidic protein (GFAP). Whereas mature astrocytes do not normally divide, a subpopulation of the reactive GFAP+ cells does so, prompting the question of whether the proliferating GFAP+ cells arise from endogenous glial progenitors or from mature astrocytes that start to proliferate in response to brain injury. Here we show by genetic fate mapping and cell type-specific viral targeting that quiescent astrocytes start to proliferate after stab wound injury and contribute to the reactive gliosis and proliferating GFAP+ cells. These proliferating astrocytes remain within their lineage in vivo, while a more favorable environment in vitro revealed their multipotency and capacity for self-renewal. Conversely, progenitors present in the adult mouse cerebral cortex labeled by NG2 or the receptor for the platelet-derived growth factor (PDGFRα) did not form neurospheres after (or before) brain injury. Taken together, the first fate-mapping analysis of astrocytes in the adult mouse cerebral cortex shows that some astrocytes acquire stem cell properties after injury and hence may provide a promising cell type to initiate repair after brain injury.

Subfields: Developmental Neuroscience, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/d568119f2264bed1be939a0b4a530bdb3550a536

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Citations in the corpus

In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model (2013, background): “NeuroD1 Reprograms NG2 Cells into Glutamatergic and GABAergic Neurons NG2 cells are the major proliferative glial cells in the adult brain under normal physiological conditions (Buffo et al., 2008; Kang et al., 2010).”
Astrocytes: biology and pathology (2009, background): “The source of newly divided scar-forming astrocytes is not well established, and may include mature astrocytes that re-enter the cell cycle as well as progenitor cells in the local parenchyma or in the periventricular regions [30, 33, 37, 77, 133, 141, 226].”
Glial Scar Borders Are Formed by Newly Proliferated, Elongated Astrocytes That Interact to Corral Inflammatory and Fibrotic Cells via STAT3-Dependent Mechanisms after Spinal Cord Injury (2013, background): “Our findings do not exclude that after genetic modulation or stimulation, reactive proliferating astroglial progenitors can be induced to adopt multipotent potential and give rise to neurons as well as glia in vitro and in vivo (Buffo et al., 2008; Robel et al., 2011).”
Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity (2009, result): “, and also consistent with another study in which NG2+ cells isolated from lesioned adult mouse brain failed to generate neurosphere”
CNS-Resident Glial Progenitor/Stem Cells Produce Schwann Cells as well as Oligodendrocytes during Repair of CNS Demyelination (2010, neutral): “Several studies have described the ability of adult parenchymal astrocytes to adopt a multipotent stem cell-like phenotype after injury (Buffo et al., 2008; Steindler and Laywell, 2003).”
Origin of new glial cells in intact and injured adult spinal cord. (2010, background): “However, cortical astrocytes can give rise to neurospheres after injury (Buffo et al., 2008).”
In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells. (2010, methodology): “To examine which of these populations would give rise to selfrenewing, multipotent neurospheres, single cells of each sorted cell population were plated in single wells to ensure clonality of the spheres (Buffo et al., 2008) and the number of neurospheres (defined as cell clusters exceeding 50 mm in”
BRAIN REGENERATION IN PHYSIOLOGY AND PATHOLOGY: THE IMMUNE SIGNATURE DRIVING THERAPEUTIC PLASTICITY OF NEURAL STEM CELLS (2011, background): “All of them act, in defined experimental conditions, as multipotent progenitor cells but differ in their origin: reactive astrocytes are of the astroglial origin, pericytes are either mesodermal or neural crest-derived, and NG2 glia are derived from the neuroectoderm (18, 25, 30, 51, 58, 59, 94, 158”
Astrocyte reactivity and reactive astrogliosis: costs and benefits. (2014, background): “When such astrocytes are isolated and cultured in vitro, some are capable of forming neurospheres that contain self-renewing and multipotent cells (32, 127).”
Astrocytes: a central element in neurological diseases (2016, background): “Neural stem cells in the subventricular zone and in the dentate gyrus of the hippocampus, the two neurogenic regions of the adult brain, express glial fibrillary acidic protein (GFAP) and it has been proposed that many of these GFAP-positive astrocytes possess stem cell properties [28, 51, 54, 55].”
Lake-front property: a unique germinal niche by the lateral ventricles of the adult brain. (2011, positive): “It has been suggested that a wounding stimulus elsewhere in the brain may create a temporarily permissive environment that resembles the stem cell niche, but the signals involved in this environment are unknown (Buffo et al., 2008).”