Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GATA3 enhances the neurogenic potential of primary human astrocytes after traumatic injury [exp1]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE116662 | GEO | 2019/02/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

GATA3 enhances the neurogenic potential of primary human astrocytes after traumatic injury [exp2]

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

Expression data from region-specific postnatal astrocytes

Project description:Astroglial cells in the adult brain constitute a heterogeneous population endowed with region-specific properties. Recently, they have acquired greater relevance as active components of the adult neural stem cell (aNSC) niches. Astrocytes located in the vicinity of aNSC reservoirs are thought to regulate aNSC behaviour. We have compared the function of glial cells isolated from the postnatal and adult subventricular zone and hippocampus (two stem cell niches, where aNSCs self-renew and give rise to immature neurons), from the olfactory bulb (a neurogenic region where the immature neurons cease to proliferate and terminally differentiate) and from a non-stem and non-neurogenic area such as the ventral mesencephalon. Co-culture experiments demonstrate that subventricular zone glial cells secrete soluble signals that promote NSC self-renewing divisions. We used microarrays to detail the global gene expression of astroglial cells isolated from four different brain regions (olfactory bulb, ventral mesencephalon, hippocampus and subventricular zone) and identified up-regulated genes coding for secreted proteins in astrocytes from the subventricular zone. Primary astrocytes were cultured from four CD-1 mouse brain regions and cells were employed for RNA extraction and hybridization on Affymetrix microarrays. Primary tissue for the astrocyte cultures was dissected from four postnatal day 3 littermate pups. The tissue from the three pups was pooled in order to reduce individual differences of expression profiles.

2012-05-31 | E-GEOD-36456 | biostudies-arrayexpress

Activation of a neural stem cell transcriptional program in parenchymal astrocytes

Project description:Neural stem cells, located in discrete niches in the adult brain, generate new neurons throughout life. These stem cells are specialized astrocytes, but astrocytes in other brain regions (parenchymal astrocytes) do not generate neurons under physiological conditions. After stroke, however, astrocytes in the mouse striatum undergo neurogenesis, triggered by decreased Notch signaling. Notch signaling can be experimentally depleted in mice by deleting the Notch-mediating transcription factor Rbpj. This dataset consists of single-cell RNA sequencing data of astrocytes isolated from the striatum (where astrocytes undergo neurogenesis in response to Rbpj deletion) or somatosensory cortex (where astrocytes don't complete neurogenesis in response to Rbpj deletion) of 4 mice. Cells were isolated from Cx30-CreER; R26-tdTomato; Rbpj(fl/fl) mice at three time points after tamoxifen-induced Rbpj deletion (2, 4, 8 weeks), and from Cx30-CreER; R26-tdTomato mice with intact Rbpj 3 days after tamoxifen. These time points span the transition from astrocyte through transit-amplifying cells to neuroblasts. The dataset contains 1) astrocytes from the striatum that initiate a neurogenic transcriptional program in response to Rbpj deletion and generate transit-amplifying cells and neuroblasts, and 2) astrocytes from the somatosensory cortex that initiate a neurogenic program in response to Rbpj deletion but fail to generate transit-amplifying cells or neuroblasts.

2020-08-01 | E-MTAB-9268 | biostudies-arrayexpress

Dual and separable roles for Ezh2 in neurogenic astroglia

Project description:The epigenetic mechanisms that enable specialized astrocytes to retain neurogenic competence throughout adult life are still poorly understood. Here we show that astrocytes that serve as neural stem cells (NSCs) in the adult mouse subventricular zone (SVZ) express the histone methyltransferase EZH2. This Polycomb repressive factor is required for neurogenesis independent of its role in SVZ NSC proliferation, as Ink4a/Arf-deficiency in Ezh2-deleted SVZ NSCs rescues cell proliferation, but neurogenesis remains defective. Olig2 is a direct target of EZH2, and repression of this bHLH transcription factor is critical for neuronal differentiation. Furthermore, Ezh2 prevents the inappropriate activation of genes that specify non-SVZ neuronal subtypes. In the human brain, SVZ cells including local astroglia also express EZH2, correlating with postnatal neurogenesis. Thus, EZH2 is an epigenetic regulator that distinguishes neurogenic SVZ astrocytes, orchestrating distinct and separable aspects of adult stem cell biology, which has important implications for regenerative medicine and oncogenesis. Examination of histone modifications (H3K27me3 and H3K4me3) in subventricular zone neural stem cells

2014-05-02 | E-GEOD-56394 | biostudies-arrayexpress

Activation of quiescent neurogenic niches of aging brain

Project description:Proposals for induced glia-to-neuron conversion have raised the potential for generating new neurons to replace those lost due to injury, aging or neurodegenerative diseases. Here, single-cell spatial transcriptomics [Multiplexed Error Robust Fluorescence In Situ Hybridization (MERFISH)] is used to construct a spatial cell atlas of the subventricular and dentate gyrus neurogenic niches of young and aged adult murine brain. RNAs that encode the RNA binding protein Polypyrimidine Tract-Binding Protein (PTBP1) in the aged murine brain are determined to be highest in glia that line previously active neurogenic niches. A glial cell population with ependymal character within an initially quiescent subventricular neurogenic niche in the aged murine brain is identified that upon transient suppression of PTBP1 reenters the cell cycle, replicates DNA, and converts into neurons through a canonical adult neurogenesis pathway. Glia-derived neurons migrate from this niche, with some neurons transiting to the striatum and acquiring a transcriptome characteristic of GABAergic inhibitory neurons. Similar PTBP1 expressing quiescent glia are identified in the corresponding neurogenic niche of aged human brain. Thus, transient reduction of PTBP1 holds potential for inducing the generation of new neurons in quiescent neurogenic niches of the aged nervous system, thereby offering promising therapeutic applications.

2024-01-09 | GSE252835 | GEO

Senolytics improve the neurogenic potential of non-glial progenitors and neurorepair in the dorsal pallium of aged killifish independent of inflammation

Project description:With advancing age, senescent cells accumulate as they are not efficiently cleared by the immune system anymore. Via a senescence-associated secretory phenotype, chronic senescent cells alter the microenvironment, creating an unfavorable milieu for neurogenesis and neurorepair. Using an innovative and rapid aging model, the African turquoise killifish, we have previously demonstrated a dramatic decline in neurogenic potential of non-glial progenitors with age. Even after traumatic brain injury, progenitor proliferation and neuron production was very low in aged killifish in comparison to young adult killifish, and overall neurorepair was incomplete. In the present study, we validated if the senolytic cocktail dasatinib and quercetin (D+Q) could reboot the neurogenic output by clearing chronic senescent cells from the aged killifish brain to re-create the necessary supportive environment. Our results confirm that the aged killifish telencephalon holds a very high senescent cell burden, which we could diminish by short-term systemic D+Q treatment. As a consequence of D+Q administration, proliferation of non-glial progenitors increased and more new neurons were generated and migrated into the parenchyma after injury. Injury-induced inflammation and glial scarring, a phenomenon only seen in aged killifish, remained unaltered. Senolytic treatment with D+Q might thus hold promise for improving brain function in aged populations, and is especially interesting for reviving the neurogenic potential of an already aged central nervous system.

2023-07-20 | PXD036437 | Pride

Comprehensive proteome of the adult neural stem cell niche identifies key regulators of adult neurogenesis

Project description:Neural stem cells (NSCs) generating new neurons are restricted to few niches in the adult mammalian brain, while the remainder rather promotes gliogenesis. Here we take advantage of the spatial separation of an NSC niche (the subependymal zone) and the region to where the newly generated neurons migrate and integrate (the olfactory bulb). Using state-of-the-art mass spectrometry we present a comprehensive proteomic characterization of these niches compared to a region of the normal brain parenchyma (cerebral cortex) that is not contusive to neurogenesis and new neuron integration. We find unique compositions of regulatory ECM components in the neurogenic niche, with quiescent NSCs as a main source of their local ECM, including the multi-functional enzyme transglutaminase 2 that we identify as crucial for neurogenesis. Atomic force microscopy further corroborates indications from the proteome that neurogenic niches are significantly stiffer than the non-neurogenic parenchyma, highlighting the unique properties of these special niches.

2020-01-27 | PXD016632 | Pride

Transcription profiling of mouse functionally distinct radial glial subsets

Project description:Since the discovery of radial glia as the source of neurons, their heterogeneity in regard to neurogenesis has been described by clonal and time-lapse analysis in vitro. However, the molecular determinants specifying neurogenic radial glia differently from radial glia that mostly self-renew remain ill-defined. Here, we isolated two radial glial subsets that co-exist at mid-neurogenesis in the developing cerebral cortex and their immediate progeny. While one subset generates neurons directly, the other is largely non-neurogenic but also gives rise to Tbr2-positive basal precursors, thereby contributing indirectly to neurogenesis. Isolation of ; these distinct radial glia subtypes allowed determining interesting differences in their transcriptome. These transcriptomes were also strikingly different from the transcriptome of radial glia isolated at the end of neurogenesis. This analysis therefore identifies, for the first time, the lineage origin of basal progenitors and the molecular differences of this lineage in comparison to directly neurogenic and gliogenic radial glia. Experiment Overall Design: Comparison of radial glial subtypes

2008-06-18 | E-GEOD-8034 | biostudies-arrayexpress

Expression data from region-specific postnatal astrocytes

2012-06-01 | GSE36456 | GEO

Dual and separable roles for Ezh2 in neurogenic astroglia

2014-05-02 | GSE56394 | GEO