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Ventral midbrain-type neural stem/precursor cells (VM-NSCs) derived from human midbrain organoids as a stable source for treating symptoms of Parkinson’s disease

ABSTRACT: Ventral midbrain-type neural stem/precursor cells (VM-NSCs) derived from human midbrain organoids as a stable source for treating symptoms of Parkinson’s disease

PROVIDER: PRJNA602673 | ENA |

REPOSITORIES: ENA

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Ventral midbrain-type neural stem/precursor cells (VM-NSCs) derived from human midbrain organoids as a stable source for treating symptoms of Parkinson’s disease

Project description:In this study, midbrain-like organoids were yielded from hPSCs to prepare cells suitable for PD therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into mDA neurons, and an unprecedentedly high proportion express midbrain-specific factors.

2020-01-23 | GSE144062 | GEO

Ventral midbrain-type neural stem/precursor cells (VM-NSCs) derived from human midbrain organoids as a stable source for treating symptoms of Parkinson’s disease

Project description:In this study, midbrain-like organoids were yielded from hPSCs to prepare cells used for PD therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into mDA neurons, and an unprecedentedly high proportion express midbrain-specific factors.

2020-02-29 | GSE142505 | GEO

Effects of Lin28a overexpression on gene expression changes during culturing neural stem cells (NSCs) derived from mouse embryonic ventral midbrain (VM)

Project description:Purpose: we want to see gene expression changes during in vitro expansion of VM-derived NSCs (VM-NSCs) with cell passges in the absence or presence of Lin28a overexpression. changes upon Lin28 overexpression in P1 and P3 stages of Neural stem cells.

2016-08-11 | GSE77851 | GEO

Ventral midbrain-type neural stem/precursor cells (VM-NSCs) derived from human midbrain organoids as a stable source for treating symptoms of Parkinson’s disease

Project description:Ventral midbrain-type neural stem/precursor cells (VM-NSCs) derived from human midbrain organoids as a stable source for treating symptoms of Parkinson’s disease

| PRJNA597220 | ENA

Effects of Lin28a overexpression on gene expression changes during culturing neural stem cells (NSCs) derived from mouse embryonic ventral midbrain (VM)

2016-08-11 | E-GEOD-77851 | biostudies-arrayexpress

Identifying secreted biomarkers of dopaminergic ventral midbrain progenitor cells

Project description:Ventral midbrain (VM) dopaminergic progenitor cells derived from human pluripotent stem cells have the potential to replace endogenously lost dopamine neurons and are currently in preclinical and clinical development for treatment of Parkinson’s Disease (PD). However, one main challenge in the quality control of the cells is that rostral and caudal VM progenitors are extremely similar transcriptionally though only the caudal VM cells give rise to dopaminergic neurons with functionality in PD. Therefore, it is critical to develop assays which can rapidly and reliably discriminate rostral from caudal VM cells during clinical manufacturing. Here, we applied shotgun proteomics to search for novel secreted biomarkers specific for caudal VM progenitors compared to rostral VM progenitors and validated key hits by ELISA. From this, we identified novel secreted markers (CPE, LGI1 and PDGFC) significantly enriched in caudal versus rostral VM progenitor cultures, whereas the markers CNTN2 and CORIN were significantly enriched in rostral VM cultures. With this data, we suggest and test in clinical grade samples a panel of coupled ELISA assays that can be applied as a quality control tool for assessing the correct patterning of cells during clinical manufacturing.

2023-12-13 | PXD039510 | Pride

Single Nucleus Transcriptomes from the Ventral Midbrain of Opioid Overdose Cases and Controls

Project description:Dynamic interactions of neurons and glia in the ventral midbrain (VM) mediate reward and addiction behavior. We studied gene expression in 212,713 VM single nuclei from 95 human opioid overdose cases and drug-free controls. Chronic exposure to opioids left numerical proportions of VM glial and neuronal subtypes unaltered, while broadly affecting glial transcriptomes, involving 9.5 - 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes, with prominent activation of the immune response including interferon, NFkB signaling, and cell motility pathways, sharply contrasting with down-regulated expression of synaptic signaling and plasticity genes in VM non-dopaminergic neurons. VM transcriptomic reprogramming in the context of opioid exposure and overdose included 325 genes with genetic variation linked to substance use traits in the broader population, thereby pointing to heritable risk architectures in the genomic organization of the brain’s reward circuitry.

2023-08-18 | GSE240457 | GEO

Single-cell transcriptional and functional analysis of human dopamine neurons in 3D fetal ventral midbrain organoid like cultures

Project description:Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain DA neurons from pluripotent stem cells (PSCs) for application in disease modeling, diagnostics, drug screening, and cell-based therapies for Parkinson’s Disease. An increased understanding of the timing and molecular mechanisms promoting the generation of distinct subtypes of midbrain DA during normal development will be essential for guiding future efforts to precisely generate molecularly defined and subtype-specific DA neurons from pluripotent stem cells. In this study, we used droplet-based single-cell RNA sequencing (scRNA-seq) to transcriptionally profile fetal DA neurons from human embryos at different stages of ventral midbrain (VM) development (6, 8, and 11 weeks post-conception) and primary fetal 3D cultures thereof that allowed differentiation and functional maturation of human DA neurons. This approach allowed us to define the molecular identities of distinct human DA progenitors and neurons at single-cell resolution and construct developmental trajectories of cell types in the developing fetal VM. Overall, these findings provide a unique transcriptional profile of developing human fetal VM and functionally mature human DA neurons, which can be used to guide stem cell-based therapies and disease modeling approaches in PD.

2022-11-16 | GSE192405 | GEO

Transcription profiling of human neural progenitor cells (hNPC) derived from the developing cortex (CTX) and ventral midbrain (VM)

Project description:Neural progenitor cells (hNPC) derived from the developing human brain can be expanded in culture and subsequently differentiated into neurons and glia. They provide an interesting source of tissue for both modeling brain development and future cellular replacement therapies. It is becoming clear that hNPC are regionally and temporally specified depending on which brain region they were isolated from and its developmental stage. We show here that hNPC derived from the developing cortex (hNPCCTX) and ventral midbrain (hNPCVM) have similar morphological characteristics and express the progenitor cell marker nestin. However, hNPCCTX cultures were highly proliferative and produced large numbers of neurons, while hNPCVM divided slowly and produced less neurons but more astrocytes. Microarray analysis revealed a similar expression pattern for some stemness markers between the two growing cultures, overlaid with a regionally specific profile that identified some important differentially expressed neurogenic transcription factors. By over expressing one of these, the transcription factor ASCL1, we were able to regain neurogenesis from hNPCVM cultures which produced larger neurons with more neurites than hNPCCTX, but no fully mature dopamine neurons. Thus hNPC are regionally specified and can be induced to undergo neurogenesis following genetic manipulation. While this restores neuronal production with a region specific phenotype, it does not restore full neurochemical maturation which may require additional factors. Experiment Overall Design: G001 and G002 are neural progenitor cells derived from human (German) embryos 8-10 wk old. Experiment Overall Design: After abortion,the cortex and ventral midbrain have been dissected and grown as neurospheres. Experiment Overall Design: 4 samples total: G001CTX, G001VM, G002CTX, G002VM

2009-01-14 | E-GEOD-13307 | biostudies-arrayexpress

Differentiation of astrocytes with characteristics of ventral midbrain from human embryonic stem cells

Project description:We hypothesized that overexpression of NFIB in the NPCs specified to VM fate can lead to generation of the astrocytes with the same regional identity. Our results presented here demonstrate that fine modulation of WNT and Sonic Hedgehog (SHH) signals during neural differentiation gave rise to NPCs with VM fate, and NFIB overexpression transformed them to astrocytes with the same regional identity.

2022-05-22 | GSE203345 | GEO

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