Stage-specific transcriptome analysis during differentiation from pluripotency to glial restricted progenitor stages
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE117664 | GEO | 2018/07/26
REPOSITORIES: GEO
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Project description:Stage-specific transcriptome analysis during differentiation from pluripotency to glial restricted progenitor stages
| PRJNA482846 | ENA
Project description:The central nervous system (CNS) is home to neuronal and glial cells. Traditionally, glia was disregarded as just the structural support across the brain and spinal cord, in striking contrast to neurons, always considered critical players in CNS functioning. In modern times this outdated dogma is continuously repelled by new evidence unravelling the importance of glia in neuronal maintenance and function. Therefore, glia replacement has been considered a potentially powerful therapeutic strategy. Glial progenitors are at the center of this hope, as they are the source of new glial cells. Indeed, sophisticated experimental therapies and exciting clinical trials shed light on the utility of exogenous glia in disease treatment. Therefore, this review article will elaborate on glial-restricted progenitor cells (GRPs), their origin and characteristics, available sources, and adaptation to current therapeutic approaches aimed at various CNS diseases, with particular attention paid to myelin-related disorders with a focus on recent progress and emerging concepts. The landscape of GRP clinical applications is also comprehensively presented, and future perspectives on promising, GRP-based therapeutic strategies for brain and spinal cord diseases are described in detail.
| S-EPMC10935984 | biostudies-literature
Project description:Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, causing motor neuron and skeletal muscle loss and death. One of the promising therapeutic approaches is stem cell graft application into the brain; however, an immune reaction against it creates serious limitations. This study aimed to research the efficiency of glial restricted progenitors (GRPs) grafted into murine CNS (central nervous system) in healthy models and the SOD1G93A ALS disease model. The cellular grafts were administered in semiallogenic and allogeneic settings. To investigate the models of immune reaction against grafted GRPs, we applied three immunosuppressive/immunomodulatory regimens: preimplantation factor (PiF); Tacrolimus; and CTLA-4, MR1 co-stimulatory blockade. We tracked the cells with bioluminescence imaging (BLI) in vivo to study their survival. The immune response character was evaluated with brain tissue assays and multiplex ELISA in serum and cerebrospinal fluid (CSF). The application of immunosuppressive drugs is disputable when considering cellular transplants into the immune-privileged site/brain. However, our data revealed that semiallogenic GRP graft might survive inside murine CNS without the necessity to apply any immunomodulation or immunosuppression, whereas, in the situation of allogeneic mouse setting, the combination of CTLA-4, MR1 blockade can be considered as the best immunosuppressive option.
| S-EPMC8308088 | biostudies-literature
Project description:The goals of this study are to compare transcriptome of NGS-derived induced oligodendrocyte progenitor cells (RNA-seq)
2019-04-20 | GSE130063 | GEO
Project description:BackgroundCell transplantation-based treatments for neurological disease are promising, yet graft rejection remains a major barrier to successful regenerative therapies. Our group and others have shown that long-lasting tolerance of transplanted stem cells can be achieved in the brain with systemic application of monoclonal antibodies blocking co-stimulation signaling. However, it is unknown if subsequent injury and the blood-brain barrier breach could expose the transplanted cells to systemic immune system spurring fulminant rejection and fatal encephalitis. Therefore, we investigated whether delayed traumatic brain injury (TBI) could trigger graft rejection.MethodsGlial-restricted precursor cells (GRPs) were intracerebroventricularly transplanted in immunocompetent neonatal mice and co-stimulation blockade (CoB) was applied 0, 2, 4, and 6 days post-grafting. Bioluminescence imaging (BLI) was performed to monitor the grafted cell survival. Mice were subjected to TBI 12 weeks post-transplantation. MRI and open-field test were performed to assess the brain damage and behavioral change, respectively. The animals were decapitated at week 16 post-transplantation, and the brains were harvested. The survival and distribution of grafted cells were verified from brain sections. Hematoxylin and eosin staining (HE) was performed to observe TBI-induced brain legion, and neuroinflammation was evaluated immunohistochemically.ResultsBLI showed that grafted GRPs were rejected within 4 weeks after transplantation without CoB, while CoB administration resulted in long-term survival of allografts. BLI signal had a steep rise following TBI and subsequently declined but remained higher than the preinjury level. Open-field test showed TBI-induced anxiety for all animals but neither CoB nor GRP transplantation intensified the symptom. HE and MRI demonstrated a reduction in TBI-induced lesion volume in GRP-transplanted mice compared with non-transplanted mice. Brain sections further validated the survival of grafted GRPs and showed more GRPs surrounding the injured tissue. Furthermore, the brains of post-TBI shiverer mice had increased activation of microglia and astrocytes compared to post-TBI wildtype mice, but infiltration of CD45+ leukocytes remained low.ConclusionsCoB induces sustained immunological tolerance towards allografted cerebral GRPs which is not disrupted following TBI, and unexpectedly TBI may enhance GRPs engraftment and contribute to post-injury brain tissue repair.
| S-EPMC8088005 | biostudies-literature
Project description:Transplanted glial-restricted progenitor (GRP) cells have potential to focally replace defunct astrocytes and produce remyelinating oligodendrocytes to avert neuronal death and dysfunction. However, most central nervous system cell therapeutic paradigms are hampered by high initial cell death and a host anti-graft immune response. We show here that composite hyaluronic acid-based hydrogels of tunable mechanical strengths can significantly improve transplanted GRP survival and differentiation. Allogeneic GRPs expressing green fluorescent protein and firefly luciferase were scaffolded in optimized hydrogel formulations and transplanted intracerebrally into immunocompetent BALB/c mice followed by serial in vivo bioluminescent imaging and chemical exchange saturation transfer magnetic resonance imaging (CEST MRI). We demonstrate that gelatin-sensitive CEST MRI can be exploited to monitor hydrogel scaffold degradation in vivo for ∼5 weeks post transplantation without necessitating exogenous labeling. Hydrogel scaffolding of GRPs resulted in a 4.5-fold increase in transplanted cell survival at day 32 post transplantation compared to naked cells. Histological analysis showed significant enhancement of cell proliferation as well as Olig2+ and GFAP+ cell differentiation for scaffolded cells compared to naked cells, with reduced host immunoreactivity. Hence, hydrogel scaffolding of transplanted GRPs in conjunction with serial in vivo imaging of cell survival and hydrogel degradation has potential for further advances in glial cell therapy.
| S-EPMC9440547 | biostudies-literature
Project description:GP protects oxidative stress-induced cell damage. The goals of this study are to compare NGS-derived transcriptome profiling (RNA-seq) with or without cGP in human neural stem cells
2022-12-31 | GSE185324 | GEO
Project description:Next-generation sequencing (NGS) has revolutionized systems-based analysis of gene expression. The goals of this study are to compare the different transcripts between control or Histone H3.3 knockdown in the neural stem cells.
2016-12-22 | GSE92720 | GEO
Project description:The goals of this research are three-fold: (i) One is to identify genetic changes associated with tumorgenesis that interfere with the ability of transformed glial cells to differentiate. This is connected with (ii) our analysis of the regulation of differentiation in normal glial progentor cells, as only by understanding this in normal cells can we understand what is occurring when differentiation fails in transformed versions of the same cells. (iii) The third is to identify the molecular basis for the greater resistance of transformed glial progenitor cells to chemotherapeutic agents as compared with normal glial progenitor cells. Thus, analysis of the populations provided will yield data crucial to two of our central areas of research, as awarded by NINDS in "Oligodendrocytes & precursors: toxicity of chemotherapy" (5R01NS044701), and "Low-level toxicant perturbation of neural cell function" (1R01ES012708). Our ability to work with essentially unlimited numbers of primary progenitor cells and transformed derivatives of these cells offers one of the few systems in which side-by-side comparison of normal and transformed cells at both the biochemical and molecular levels is possible. Using defined cell populations, expression profiles will be compared to reveal changes in cell type specific markers and regulatory factors associated with transformation. In addition, retention of markers despite transformation may enable identification of new markers useful in the diagnosis of glial tumors. Transformation of glial progenitor cells is associated both with loss of the proteins required for normal differentiation and with an inability to normally activate proteins that function in differentiation control. By side-by-side analysis of gene expression in normal and transformed glial progenitor cells, and analysis of the response to inducers of differentiation in each these populations, we will identify candidate regulators critical in the control of normal differentiation. Identification of these regulators will also provide clues as to overcome the blockade of differentiation that occurs in glial cancers (which represent the majority of adult brain tumors). RNA will be isolated from two separate preparations of glial progenitors. Preparation of purified populations has been described in multiple of our previous publications (Mayer, M. et al. (1994) Development 120, 142-153; Mayer-Pröschel, M. et al. (1997) Neuron 19, 773-785; Rao, M. and Mayer-Pröschel, M. (1997) Dev. Biology 188, 48-63). Total RNA from purified cell cultures will be extracted in a two step process. RNA will first be extracted by dounce homogenization in phenol/guanidine isothiocyonate solution (Trizol, Invitrogen, California) followed by isopropanol precipitation. Contaminating traces of DNA and protein will then be removed by silica-based affinity chromatography and Dnase treatment (NucleoSpin RNA Purification system, Clontech, California). Depending on the cell type, 5x105 cells will typically yield 5-15µg of high quality RNA (OD260/280=2.1 at pH7.5). In order to determine purity and molecular weight distribution, samples will be routinely tested on a Agilent Bioanalyzer. cDNA will be generated from total RNA and then be submitted to one round of amplification and labeling using the messageAmp system (Ambion). Probes are then hybridized to the Affymerix Rat 230 (A/B or 2.0) GeneChip expression array. Array data will be processed using the Micro Array Suite 5.0 (MAS, Affymetrix). .Cel files containing normalized, relative expression data for all genes tested will be used for downstream statistical analysis.
2008-06-16 | E-GEOD-9763 | biostudies-arrayexpress
Project description:Next-generation sequencing (NGS) has revolutionized systems-based analysis of gene expression. The goals of this study are to compare the different transcripts between TRPM2 knockdown and control in the neural progenitor cells when the maternal hyperthermia was induced.
2017-10-26 | GSE106165 | GEO