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3D Model Enhances Human Glia conversion to Neurons with Dopaminergic Functional and Molecular Traits Or: 3D Model Enhances Human Glia conver-sion to Induced Dopamine Neurons?

ABSTRACT: 3D Model Enhances Human Glia conversion to Neurons with Dopaminergic Functional and Molecular Traits Or: 3D Model Enhances Human Glia conver-sion to Induced Dopamine Neurons?

PROVIDER: PRJNA1011300 | ENA |

REPOSITORIES: ENA

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3D Model Enhances Human Glia conversion to Neurons with Dopaminergic Functional and Molecular Traits Or: 3D Model Enhances Human Glia conver-sion to Induced Dopamine Neurons?

Project description:Parkinson’s disease (PD), a prevalent neurodegenerative disorder, is primarily characterized by progressive loss of ventral midbrain dopamine (DA) neurons. This focal degeneration makes PD suitable for cell replacement therapies and clinical trials using stem cell derived-DA neurons are ongoing. An emerging alternative to cell transplantation for brain repair is in vivo reprogramming, where resident glia is converted into neurons directly inside the brain. While functional neurons with potential therapeutic effects can be obtained via in vivo conversion in rodent studies, translating this to relevant human pre-clinical models has been limited to two-dimensional (2D) cultures. To mimic three-dimensional (3D) complexity and approximate in vivo-like conversion, we developed a 3D model for human glia conversion. Our model promotes neural conversion and generates functionally mature DA neurons at a faster pace than in 2D. Molecular profiling, single-nucleus transcriptomics and lineage tracing mapped glia heterogeneity, provided mechanistic insights of the reprogramming process and defined neuronal identity after conversion. Our results emphasize the advantages of utilizing 3D models as a reproducible and con-sistent platform for reprogramming studies.

2024-10-15 | GSE242076 | GEO

Local and global influences on protein turnover in neurons and glia.

Project description:Proteins exhibit dynamics in their expression level in response to intracellular and extracellular signals. Regulation of protein turnover allows cells to rapidly and efficiently remodel their proteomes. It is known that proteins can show very different turnover rates in different tissue of the same organism, but little is known about protein turnover rates in different brain cell types. We used a dynamic SILAC approach to determine protein half-lives in primary hippocampal cultures (containing a mixture of neurons and glia cells) as well as in neuron-enriched and glia-enriched cultures. We determined the protein half-lives for over 5100 proteins and found half-lives ranging from <1 to > 20 days with a median half-life of 5.4 days in mixed cultures. Membrane proteins as a group were shorter-lived and mitochondrial proteins, surprisingly, were longer-lived. Proteins in glia possessed significantly shorter half-lives than the same proteins in neurons. The presence of glia sped up or slowed down the half-lives of neuronal proteins. Our results demonstrate that both the cell-type of origin as well as the nature of the extracellular environment have potent influences on protein turnover.

2018-06-05 | PXD008596 | Pride

Differential Nucleosome Spacing in Neurons and Glia

Project description:Differential Nucleosome Spacing in Neurons and Glia

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3D Biocomposite Culture Enhances Differentiation of Dopamine-like Neurons from SH-SY5Y cells: A Model for Studying Parkinson’s Disease Phenotypes

Project description:Studies of underlying neurodegenerative processes in Parkinson’s Disease (PD) have traditionally utilized cell cultures grown on two-dimensional (2D) surfaces. Biomimetic three-dimensional (3D) cell culture platforms have been developed to better emulate features of the brain’s natural microenvironment. We here use our bioengineered brain-like tissue model, composed of a silk-hydrogel composite, to study the 3D microenvironment’s contributions on the development and performance of dopaminergic-like neurons (DLNs). Compared with 2D culture, SH-SY5Y cells differentiated in 3D microenvironments were enriched for DLNs concomitant with a reduction in proliferative capacity during the neurodevelopmental process. Additionally, the 3D DLN cultures were more sensitive to oxidative stresses elicited by the PD-related neurotoxin 1-methyl-4-phenylpyridinium (MPP). MPP induced transcriptomic profile changes specific to 3D-differentiated DLN cultures, replicating the dysfunction of neuronal signaling pathways and mitochondrial dynamics implicated in PD. Overall, this physiologically-relevant 3D platform resembles a useful tool for studying dopamine neuron biology and interrogating molecular mechanisms underlying neurodegeneration in PD.

2022-10-17 | GSE203522 | GEO

3D Biocomposite Culture Enhances Differentiation of Dopamine-like Neurons from SH-SY5Y cells: A Model for Studying Parkinson’s Disease Phenotypes

Project description:3D Biocomposite Culture Enhances Differentiation of Dopamine-like Neurons from SH-SY5Y cells: A Model for Studying Parkinson’s Disease Phenotypes

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Effect of chronic mechanical compression on co-cultures of human induced neurons and murine glia

Project description:Human induced neurons and primary murine glia were subjected to a controlled in vitro model of mechanical compression to determine how solid stress—similar to forces present in glioblastoma—directly alters neuronal and glial transcriptional programs. RNA sequencing was performed after 24 hours of compression, with species-specific alignment enabling independent analysis of neuronal and glial responses. Compressed human neurons showed strong activation of hypoxia-responsive metabolic genes, pro-inflammatory signaling pathways, and intrinsic apoptotic programs. Murine glia exhibited parallel induction of hypoxia and apoptotic pathways, accompanied by robust NF-κB/AP-1-driven inflammatory cytokine expression characteristic of astrocytic and microglial activation. These data define the conserved transcriptional responses by which neurons and glia detect and respond to solid stress, providing a resource for understanding mechanotransduction and neuroinflammatory signaling in diseases characterized by mass effect, including glioblastoma.

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Protocol for 3D direct reprogramming of human glia into dopaminergic neurons with gene expression and immunocytochemistry validation

Project description:Protocol for 3D direct reprogramming of human glia into dopaminergic neurons with gene expression and immunocytochemistry validation

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Macrophage-glia interactions regulate immune-damage to enteric neurons during West Nile virus infection [3]

Project description:Functional gastrointestinal (GI) tract disorders affect a substantial proportion of the global population and are often preceded by intestinal infections that cause injury to enteric neurons and glia through unrestrained immune responses. However, the mechanisms that limit infection-induced inflammation and protect the enteric nervous system remain poorly understood. Here, we investigated neuron-glia-macrophage interactions after West Nile virus (WNV) infection, a model neurotropic virus that causes GI tract dysmotility via injury of enteric neurons through a T cell-mediated cytolytic mechanism. In response to WNV infection, resident muscularis macrophages upregulate antiviral, proinflammatory, and immunomodulatory genes. However, pharmacological depletion of resident macrophages did not affect viral burden in the GI tract, but rather reshaped the enteric glial response to WNV, resulting in excessive production of T cell and neutrophil chemoattractants. This amplified recruitment of immune cells worsened enteric neuronal injury. Together, our findings identify resident muscularis macrophages as key regulators of glia-driven inflammation during enteric viral infection and reveal their role in protecting enteric neurons from immune-mediated damage.

2026-02-19 | GSE315459 | GEO

Macrophage-glia interactions regulate immune-damage to enteric neurons during West Nile virus infection [4]

2026-02-19 | GSE315460 | GEO

Macrophage-glia interactions regulate immune-damage to enteric neurons during West Nile virus infection [1]

2026-02-19 | GSE315454 | GEO