GATA3 enhances the neurogenic potential of primary human astrocytes after traumatic injury [exp1]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA479832 | ENA |
REPOSITORIES: ENA
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 | 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: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:We conducted snRNAseq of mouse astrocytes after traumatic spinal cord injury (SCI). These data reveal transcriptomic similarities and differences among astrocytes in healthy spinal cord and after spinal cord injury.
2024-01-09 | GSE247844 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-02-27 | GSE117907 | GEO
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
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
Project description:Brain-derived extracellular vesicles participate in inter-organ communication after traumatic brain injury by transporting pathogens to initiate secondary injury. Inflammasome related proteins encapsulated in brain-derived extracellular vesicles are capable of crossing the blood-brain barrier to reach distal tissues. These proteins initiate inflammatory dysfunction such as neurogenic heterotopic ossification. This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies. Accordingly, a rat model of neurogenic heterotopic ossification that combined traumatic brain injury and achillotenotomy was developed to address these two issues. Histological examination of the injured tendon identified the coexistence of ectopic calcification and fibroblast pyroptosis. The relationships among brain-derived extracellular vesicles, fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo. The present work highlighted the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offered a potential strategy for the prevention of neurogenic heterotopic ossification after traumatic brain injury.
2023-11-02 | PXD046626 | iProX
Project description:Traumatic brain injury (TBI) caused by external mechanical forces is a major health burden worldwide, but the underlying mechanism in glia remains largely unclear. We report herein that Drosophila adults exhibit a defective blood-brain-barrier (BBB), elevated innate immune responses, and appear to be hypertrophy of astrocytes upon consecutive strikes with a high-impact trauma device. RNA sequencing (RNA-seq) analysis of these astrocytes revealed upregulated expression of genes encoding PDGF and VEGF receptor-related (Pvr, a receptor tyrosine kinase (RTK)), adaptor protein complex 1 (AP-1, a transcription factor complex of the c-Jun N-terminal Kinase (JNK) pathway) composed of Jun-related antigen (Jra) and kayak (kay), and matrix metalloproteinase 1 (Mmp1) following TBI. Interestingly, Pvr is both required and sufficient for AP-1 and Mmp1 upregulation, while knockdown of AP-1 expression in the background of Pvr overexpression in astrocytes rescued Mmp1 upregulation upon TBI, indicating that Pvr acts as the upstream receptor for the downstream AP-1–Mmp1 transduction. Moreover, dynamin-associated endocytosis was found to be an important regulatory step in downregulating Pvr signaling. Our results identify a new Pvr–AP-1–Mmp1 signaling pathway in astrocytes in response to TBI, providing potential targets for developing new therapeutic strategies of TBI.
2024-06-30 | GSE263447 | GEO