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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

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

Differential Nucleosome Spacing in Neurons and Glia

Project description:Differential Nucleosome Spacing in Neurons and Glia

| PRJNA553209 | ENA

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

| PRJNA841191 | ENA

Single cell sequencing of radial glia progeny reveals diversity of newborn neurons in the adult zebrafish brain

Project description:Zebrafish display widespread and pronounced adult neurogenesis, which is fundamental for their regeneration capability after central nervous system injury. However, the cellular identity and the biological properties of adult newborn neurons are elusive for most brain areas. Here, we used short-term lineage tracing of radial glia progeny to prospectively isolate newborn neurons from the her4.1+ radial glia lineage in the homeostatic adult forebrain. Transcriptome analysis of radial glia, newborn neurons and mature neurons using single cell sequencing identified distinct transcriptional profiles including novel markers for each population. Specifically, we detected 2 separate newborn neuron types, which showed diversity of cell fate commitment and location. Further analyses showed homology of these cell types to neurogenic cells in the mammalian brain, identified neurogenic commitment in proliferating radial glia and indicated that glutamatergic projection neurons fate are generated in the adult zebrafish telecephalon. Thus, we prospectively isolated adult newborn neurons from the adult zebrafish forebrain, identified markers for newborn and mature neurons in the adult brain, revealed intrinsic heterogeneity among adult newborn neurons and their homology to mammalian adult neurogenic cell types.

2019-11-27 | GSE137525 | GEO

RNA-sequencing of Drosophila expressing mutant Huntingtin in neurons or glia

Project description:We performed RNA-seq on head tissue collected from Drosophila expressing N-terminal (UAS-HTTNT231Q128) or full-length (UAS-HTTFL200Q) human mHTT in neurons (elav-GAL4) or glia (repo-GAL4).

2021-06-03 | GSE157287 | GEO

Differential Nucleosome Spacing in Neurons and Glia [RNA-seq]

Project description:Differential Nucleosome Spacing in Neurons and Glia [RNA-seq]

| PRJNA552364 | ENA

NG2 glia-derived GABA release tunes inhibitory synapses and contributes to anxiety-like behavior in chronic social defeat stress

Project description:NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers an anxiety-like behavior in vivo and induces anxiety-like behavior in a mouse model of chronic social defeat stress.

2020-11-24 | GSE162049 | GEO

RNA-seq of Drosophila melanogaster neurons, glia and hemocytes at embryonic stage 16 and third instar wandering larvae

Project description:We produced bulk RNA sequencing data on Drosophila neurons, glia and hemocytes at embryonic and larval stages to extrapolate the most significant and specific features that identify a cell type as a whole. We also tracked changes in the expression in the two stages. We identified stable features that define a cell type functionally and developmentally as well as plastic features including stage-specific metabolic states, which likely depend on the environment.

2024-08-27 | E-MTAB-14413 | biostudies-arrayexpress

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