Similar Datasets
Project description:Astrocytes are an abundant cell type in the vertebrate central nervous system and can act as neural stem cells in specialized niches where they constitutively generate new neurons. Outside the stem cell niches, however, these glial cells are not neurogenic. Although injuries in the mammalian central nervous system lead to profound proliferation of reactive astrocytes (RAs), which cluster at the lesion site to form a gliotic scar, neurogenesis does not take place. Therefore, a plausible regenerative therapeutic option is to coax the RAs to form neurons as an endogenous reservoir for repair. However, little is known on the mechanisms by which regenerative neurogenesis can be induced in mammalian RAs. In zebrafish, Gata acts as a regenerative factor that induces the plasticity of glial cells after injury. However, the effects of GATA in human astrocytes are not known. Therefore, in this report, we investigated how overexpression of GATA in primary fetal human astrocytes would affect the neurogenic potential before and after injury, and determined the transcriptional regulation exerted by GATA using next-generation sequencing. We found that GATA expression in primary human astrocyte cultures is not induced after scratch injury. Lentivirus-mediated overexpression of GATA significantly increased the number of SOX- expressing neural progenitors and altered the expression levels of genes related to cell proliferation and neurogenesis. Our results suggest that GATA is sufficient for enhancing the neurogenic potential of primary human astrocytes after injury.
2019-02-27 | GSE117906 | GEO
Project description:Astrocytes are an abundant cell type in the vertebrate central nervous system and can act as neural stem cells in specialized niches where they constitutively generate new neurons. Outside the stem cell niches, however, these glial cells are not neurogenic. Although injuries in the mammalian central nervous system lead to profound proliferation of reactive astrocytes (RAs), which cluster at the lesion site to form a gliotic scar, neurogenesis does not take place. Therefore, a plausible regenerative therapeutic option is to coax the RAs to form neurons as an endogenous reservoir for repair. However, little is known on the mechanisms by which regenerative neurogenesis can be induced in mammalian RAs. In zebrafish, Gata acts as a regenerative factor that induces the plasticity of glial cells after injury. However, the effects of GATA in human astrocytes are not known. Therefore, in this report, we investigated how overexpression of GATA in primary fetal human astrocytes would affect the neurogenic potential before and after injury, and determined the transcriptional regulation exerted by GATA using next-generation sequencing. We found that GATA expression in primary human astrocyte cultures is not induced after scratch injury. Lentivirus-mediated overexpression of GATA significantly increased the number of SOX- expressing neural progenitors and altered the expression levels of genes related to cell proliferation and neurogenesis. Our results suggest that GATA is sufficient for enhancing the neurogenic potential of primary human astrocytes after injury.
2019-02-27 | GSE116662 | GEO
Project description:GATA3 enhances the neurogenic potential of primary human astrocytes after traumatic injury
| PRJNA483548 | ENA
Project description:GATA3 enhances the neurogenic potential of primary human astrocytes after traumatic injury [exp2]
| PRJNA483550 | ENA
Project description:GATA3 enhances the neurogenic potential of primary human astrocytes after traumatic injury [exp1]
| PRJNA479832 | ENA
Project description:Astrocytes are abundant cell types in the vertebrate central nervous system and can act as neural stem cells in specialized niches where they constitutively generate new neurons. Outside the stem cell niches, however, these glial cells are not neurogenic. Although injuries in the mammalian central nervous system lead to profound proliferation of astrocytes, which cluster at the lesion site to form a gliotic scar, neurogenesis does not take place. Therefore, a plausible regenerative therapeutic option is to coax the endogenous reactive astrocytes to a pre-neurogenic progenitor state and use them as an endogenous reservoir for repair. However, little is known on the mechanisms that promote the neural progenitor state after injuries in humans. Gata3 was previously found to be a mechanism that zebrafish brain uses to injury-dependent induction of neural progenitors. However, the effects of GATA3 in human astrocytes after injury are not known. Therefore, in this report, we investigated how overexpression of GATA3 in primary human astrocytes would affect the neurogenic potential before and after injury in 2D and 3D cultures. We found that primary human astrocytes are unable to induce GATA3 after injury. Lentivirus-mediated overexpression of GATA3 significantly increased the number of GFAP/SOX2 double positive astrocytes and expression of pro-neural factor ASCL1, but failed to induce neurogenesis, suggesting that GATA3 is required for enhancing the neurogenic potential of primary human astrocytes and is not sufficient to induce neurogenesis alone.
| S-EPMC6380212 | biostudies-literature
Project description:Parenchymal astrocytes have emerged as a potential reservoir for new neurons in non-neurogenic brain regions. It is currently unclear how astrocyte neurogenesis is controlled molecularly. Here we show that Notch signaling-deficient astrocytes can generate new neurons after injury. Using single-cell RNA sequencing, we found that, when Notch signaling is blocked, astrocytes transition to a neural stem cell-like state. However, only after injury do a few of these primed astrocytes unfold a neurogenic program, including a self-amplifying progenitor-like state. Further, reconstruction of the trajectories of individual cells allowed us to uncouple astrocyte neurogenesis from reactive gliosis, which occur along independent branches. Finally, we show that cortical neurogenesis molecularly recapitulates canonical subventricular zone neurogenesis with remarkable fidelity. Our study supports a widespread potential of parenchymal astrocytes to function as dormant neural stem cells.
| S-EPMC7534841 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-01-08 | E-GEOD-59647 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-14 | E-GEOD-58485 | biostudies-arrayexpress
Project description:Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these 'reactive' astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage-restricted astrocytes to either tumor necrosis factor alpha (TNF-?) (via nuclear factor-?B (NF?B)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-?1 and peroxisome proliferator-activated receptor gamma (PPAR?)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes.
| S-EPMC4937102 | biostudies-literature