In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons

Lin, Lin; Yuan, Jing; Sander, Bjoern; Golas, Monika M.

doi:10.5966/sctm.2014-0083

Cited by 36 publications

(34 citation statements)

References 70 publications

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“…While both SPN derive from the LGE 19,22-24,49 , producing fully differentiated dSPN or iSPN in vitro [77][78][79][80][81] has remained a challenge. While there was increasing evidence that distinct transcriptional programs underlie the specification of both subtypes 23, 41,45,46 , in vitro studies raised questions regarding the mechanisms controlling SPN differentiation.…”

Section: Ebf1 Deletion Affects Ispn Migration and Intermix In The Strmentioning

confidence: 99%

Active intermixing of indirect and direct neurons builds the striatal mosaic

Tinterri

Mendary

Diana

et al. 2018

Preprint

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The striatum controls behaviors via the activity of direct and indirect pathway projection neurons (dSPN and iSPN) that are intermingled in all compartments.While such mosaic ensures the balanced activity of the two pathways, how it emerges remains largely unknown. Here, we show that both SPN populations are specified embryonically and progressively intermix through multidirectional iSPN migration. Using conditional mutants of the dSPN-specific transcription factor Ebf1, we found that inactivating this gene impaired selective dSPN properties, including axon pathfinding, whereas molecular and functional features of iSPN were preserved. Remarkably, Ebf1 mutation disrupted iSPN/dSPN intermixing, resulting in an uneven distribution. Such architectural defect was selective of the matrix compartment, revealing that intermixing is a parallel process to compartment formation. Our study reveals that, while iSPN/dSPN specification is largely independent, their intermingling emerges from an active migration of iSPN, thereby providing a novel framework for the building of striatal architecture.

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Section: Ebf1 Deletion Affects Ispn Migration and Intermix In The Strmentioning

confidence: 99%

Active intermixing of indirect and direct neurons builds the striatal mosaic

Tinterri

Mendary

Diana

et al. 2018

Preprint

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“…From day 10 onwards, the cells were differentiated in NBA supplemented with 1% Penicillin/Streptomycin/Glutamine, 2% B27 supplement, 1% N2 supplement with 10 μM Forskolin, and 50 ng/mL BDNF. This is based on the protocol by Lin and colleagues [46] .…”

Section: Methodsmentioning

confidence: 99%

Conversion of adult human fibroblasts into neural precursor cells using chemically modified mRNA

Connor

Firmin

McCaughey-Chapman

et al. 2018

Heliyon

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Direct reprogramming offers a unique approach by which to generate neural lineages for the study and treatment of neurological disorders. Our objective is to develop a clinically viable reprogramming strategy to generate neural precursor cells for the treatment of neurological disorders through cell replacement therapy. We initially developed a method for directly generating neural precursor cells (iNPs) from adult human fibroblasts by transient expression of the neural transcription factors, SOX2 and PAX6 using plasmid DNA. This study advances these findings by examining the use of chemically modified mRNA (cmRNA) for direct-to-iNP reprogramming. Chemically modified mRNA has the benefit of being extremely stable and non-immunogenic, offering a clinically suitable gene delivery system. The use of SOX2 and PAX6 cmRNA resulted in high co-transfection efficiency and cell viability compared with plasmid transfection. Neural positioning and fate determinant genes were observed throughout reprogramming with ion channel and synaptic marker genes detected during differentiation. Differentiation of cmRNA-derived iNPs generated immature GABAergic or glutamatergic neuronal phenotypes in conjunction with astrocytes. This represents the first time a cmRNA approach has been used to directly reprogram adult human fibroblasts to iNPs, potentially providing an efficient system by which to generate human neurons for both research and clinical application.

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“…Disease-relevant hiPSC-based systems are obtained through guided differentiation of these NPCs usually towards neural cell types associated with the disease of interest. This process is known as ‘monolayer differentiation’, has been successful in generating various neuronal subtypes including cortical excitatory projection neurons [ 45 ] and inhibitory interneurons [ 47 ], hippocampal granule neurons [ 48 ], dopaminergic neurons [ 49 ] and striatal medium spiny neurons [ 50 ], and has proved very useful in a multitude of studies modelling neurological diseases that will be discussed in detail below.…”

Section: Investigating Synaptic Dysfunction In Hipsc-based Models Ofmentioning

confidence: 99%

Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an overview of induced pluripotent stem-cell-based disease models

et al. 2018

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Synaptic dysfunction in CNS disorders is the outcome of perturbations in physiological synapse structure and function, and can be either the cause or the consequence in specific pathologies. Accumulating data in the field of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia and bipolar disorder, point to a neurodevelopmental origin of these pathologies. Due to a relatively early onset of behavioural and cognitive symptoms, it is generally acknowledged that mental illness initiates at the synapse level. On the other hand, synaptic dysfunction has been considered as an endpoint incident in neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's, mainly due to the considerably later onset of clinical symptoms and progressive appearance of cognitive deficits. This dichotomy has recently been challenged, particularly since the discovery of cell reprogramming technologies and the generation of induced pluripotent stem cells from patient somatic cells. The creation of ‘disease-in-a-dish’ models for multiple CNS pathologies has revealed unexpected commonalities in the molecular and cellular mechanisms operating in both developmental and degenerative conditions, most of which meet at the synapse level. In this review we discuss synaptic dysfunction in prototype neurodevelopmental and neurodegenerative diseases, emphasizing overlapping features of synaptopathy that have been suggested by studies using induced pluripotent stem-cell-based systems. These valuable disease models have highlighted a potential neurodevelopmental component in classical neurodegenerative diseases that is worth pursuing and investigating further. Moving from demonstration of correlation to understanding mechanistic causality forms the basis for developing novel therapeutics.

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In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons

Cited by 36 publications

References 70 publications

Active intermixing of indirect and direct neurons builds the striatal mosaic

Active intermixing of indirect and direct neurons builds the striatal mosaic

Conversion of adult human fibroblasts into neural precursor cells using chemically modified mRNA

Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an overview of induced pluripotent stem-cell-based disease models

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