A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse

Magnusson, Jens P; Göritz, Christian; Tatarishvili, Jemal; Dias, David O.; Smith, Emma; Lindvall, Olle; Kokaia, Zaal; Frisén, Jonas

doi:10.1126/science.346.6206.237

Cited by 361 publications

(439 citation statements)

References 26 publications

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“…1F,G). Newly produced cells might not survive for any extensive period in the adult brain, and this is particularly noticeable after injury (Kernie and Parent, 2010;Magnusson et al, 2014). However, in agreement with the morphological analysis, the number of granule cells produced de novo more than doubled and these were maintained at the lesioned hemisphere 3 to 6 months after the lesion, as compared with the unlesioned hemisphere or sham control (n≥5 per time point, P<0.001; Fig.…”

Section: Cellular Recovery After Cerebellar Injurysupporting

confidence: 68%

Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration

et al. 2017

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Zebrafish can regenerate after brain injury, and the regenerative process is driven by resident stem cells. Stem cells are heterogeneous in the vertebrate brain, but the significance of having heterogeneous stem cells in regeneration is not understood. Limited availability of specific stem cells might impair the regeneration of particular cell lineages. We studied regeneration of the adult zebrafish cerebellum, which contains two major stem and progenitor cell types: ventricular zone and neuroepithelial cells. Using conditional lineage tracing we demonstrate that cerebellar regeneration depends on the availability of specific stem cells. Radial glia-like cells are thought to be the predominant stem cell type in homeostasis and after injury. However, we find that radial glia-like cells play a minor role in adult cerebellar neurogenesis and in recovery after injury. Instead, we find that neuroepithelial cells are the predominant stem cell type supporting cerebellar regeneration after injury. Zebrafish are able to regenerate many, but not all, cell types in the cerebellum, which emphasizes the need to understand the contribution of different adult neural stem and progenitor cell subtypes in the vertebrate central nervous system.

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Section: Cellular Recovery After Cerebellar Injurysupporting

confidence: 68%

Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration

et al. 2017

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“…Unravelling these features might help to unleash the full neurogenic potential of the adult brain, a fundamental prerequisite in order to design cell replacement therapies for brain repair. Interestingly, while this study was under revision the activation of neurogenic potential in striatal astrocytes was also demonstrated in a model of stroke (Magnusson et al, 2014) and under physiological conditions during guinea pig development (Luzzati et al, 2014). Thus, in contrast to SVZ and dentate gyrus neuronal progenitors, which are constitutively active, other populations of neurogenic astrocytes are activated only under specific conditions.…”

Section: Resultsmentioning

confidence: 99%

Striatal astrocytes produce neuroblasts in an excitotoxic model of Huntington's disease

et al. 2015

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In the adult brain, subsets of astrocytic cells residing in well-defined neurogenic niches constitutively generate neurons throughout life. Brain lesions can stimulate neurogenesis in otherwise non-neurogenic regions, but whether local astrocytic cells generate neurons in these conditions is unresolved. Here, through genetic and viral lineage tracing in mice, we demonstrate that striatal astrocytes become neurogenic following an acute excitotoxic lesion. Similar to astrocytes of adult germinal niches, these activated parenchymal progenitors express nestin and generate neurons through the formation of transit amplifying progenitors. These results shed new light on the neurogenic potential of the adult brain parenchyma.

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“…Indeed, astrocyte culture with a 3D collagen scaffold has also shown a reduction in cell viability [26]. In this set of experiments, we did not look at the levels of NOTCH expression which may determine differences in proliferation in astrocytes [60,61]. Further work will clarify these points in more detail.…”

Section: Discussionmentioning

confidence: 99%

Astrocytes Grown in Alvetex® Three Dimensional Scaffolds Retain a Non-reactive Phenotype

2016

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Protocols which permit the extraction of primary astrocytes from either embryonic or postnatal mice are well established however astrocytes in culture are different to those in the mature CNS. Three dimensional (3D) cultures, using a variety of scaffolds may enable better phenotypic properties to be developed in culture. We present data from embryonic (E15) and postnatal (P4) murine primary cortical astrocytes grown on coated coverslips or a 3D polystyrene scaffold, Alvetex. Growth of both embryonic and postnatal primary astrocytes in the 3D scaffold changed astrocyte morphology to a mature, protoplasmic phenotype. Embryonic-derived astrocytes in 3D expressed markers of mature astrocytes, namely the glutamate transporter GLT-1 with low levels of the chondroitin sulphate proteoglycans, NG2 and SMC3. Embroynic astrocytes derived in 3D show lower levels of markers of reactive astrocytes, namely GFAP and mRNA levels of LCN2, PTX3, Serpina3n and Cx43. Postnatal-derived astrocytes show few protein changes between 2D and 3D conditions. Our data shows that Alvetex is a suitable scaffold for growth of astrocytes, and with appropriate choice of cells allows the maintenance of astrocytes with the properties of mature cells and a non-reactive phenotype.

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A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse

Cited by 361 publications

References 26 publications

Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration

Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration

Striatal astrocytes produce neuroblasts in an excitotoxic model of Huntington's disease

Astrocytes Grown in Alvetex® Three Dimensional Scaffolds Retain a Non-reactive Phenotype

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