Fetal mouse mesencephalic NPCs generate dopaminergic neurons from post-mitotic precursors and maintain long-term neural but not dopaminergic potential in vitro

Meyer, Anne K.; Jarosch, Alexander; Schurig, Katja; Nuesslein, Ina; Kißenkötter, Stefan; Storch, Alexander

doi:10.1016/j.brainres.2012.07.034

Cited by 7 publications

(7 citation statements)

References 51 publications

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“…In conventional 2D murine NSC culture protocols, cells are routinely cultured as a monolayer on fibronectin-coated polystyrene substrates. 39 The spread cell morphology observed on planar substrates differs strikingly from the appearance of cells in brain tissue, which we tried to mimic in vitro by confining NSCs within cylindrical microtubes ( Figure 1 a). The microtube structures were fabricated by angular deposition of silicon monoxide/silicon dioxide nanomembranes onto a photolithographically structured polymer sacrificial layer and selective dissolution of the polymer.…”

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confidence: 99%

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Dimensionality of Rolled-up Nanomembranes Controls Neural Stem Cell Migration Mechanism

et al. 2015

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We employ glass microtube structures fabricated by rolled-up nanotechnology to infer the influence of scaffold dimensionality and cell confinement on neural stem cell (NSC) migration. Thereby, we observe a pronounced morphology change that marks a reversible mesenchymal to amoeboid migration mode transition. Space restrictions preset by the diameter of nanomembrane topography modify the cell shape toward characteristics found in living tissue. We demonstrate the importance of substrate dimensionality for the migration mode of NSCs and thereby define rolled-up nanomembranes as the ultimate tool for single-cell migration studies.

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confidence: 99%

“…In conventional 2D murine NSC culture protocols, cells are routinely cultured as a monolayer on fibronectin-coated polystyrene substrates . The spread cell morphology observed on planar substrates differs strikingly from the appearance of cells in brain tissue, which we tried to mimic in vitro by confining NSCs within cylindrical microtubes (Figure a).…”

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confidence: 99%

Dimensionality of Rolled-up Nanomembranes Controls Neural Stem Cell Migration Mechanism

et al. 2015

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“…In contrast, overexpression of Foxa2 results in rapid cell cycle arrest and maturation of NPCs toward DA neuronal phenotype [12]. Intriguingly, the transcription profile of NPCs has demonstrated that Foxa2 is downregulated in expansion conditions in vitro [1]. These studies indicate that the silencing of Foxa2 gene expression could impact DA neuron differentiation.…”

Section: Introductionmentioning

confidence: 91%

“…N eural precursor cells (NPCs) with self-renewal and multipotent properties can be derived from various brain regions and during various stages of development [1]. These precursor cells can differentiate into all three neural lineage cell types: neurons, astrocytes, and oligodendrocytes [2].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Activation of theFoxa2Gene Is Required for Maintaining the Potential of Neural Precursor Cells to Differentiate into Dopaminergic Neurons After Expansion

Bang

Kwon

et al. 2015

Stem Cells and Development

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Dysregulation of forkhead box protein A2 (Foxa2) expression in fetal ventral mesencephalon (VM)-derived neural precursor cells (NPCs) appears to be associated with the loss of their potential to differentiate into dopaminergic (DA) neurons after mitogenic expansion in vitro, hindering their efficient use as a transplantable cell source. Here, we report that epigenetic activation of Foxa2 in VM-derived NPCs by inducing histone hyperacetylation rescues the mitogenic-expansion-dependent decrease of differentiation potential to DA neurons. The silencing of Foxa2 gene expression after expansion is accompanied by repressive histone modifications, including hypoacetylation of histone H3 and H4 and trimethylation of H3K27 on the Foxa2 promoter, as well as on the global level. In addition, histone deacetylase 7 (HDAC7) is highly expressed during differentiation and recruited to the Foxa2 promoter. Induction of histone acetylation in VM-derived NPCs by either knockdown of HDAC7 or treatment with the HDAC inhibitor apicidin upregulates Foxa2 expression via hyperacetylation of H3 and a decrease in H3K27 trimethylation on the promoter regions, leading to the expression of DA neuron developmental genes and enhanced differentiation of DA neurons. These effects are antagonized by the expression of shRNAs specific for Foxa2 but enhanced by shRNA for HDAC7. Collectively, these findings indicate that loss of differentiation potential of expanded VM-derived NPCs is attributed to a decrease in Foxa2 expression and suggest that activation of the endogenous Foxa2 gene by epigenetic regulation might be an approach to enhance the generation of DA neurons.

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“…Neural Stem Cell Culture and Encapsulation : Primary fetal mouse neural stem cells were a gift of A. Storch (University Clinic Carl Gustav Carus Dresden) Stem cell culture was done as described previously . In short, neural stem cells were maintained in serum‐free media comprising a DMEM (high glucose)/F‐12 mixture (2:1), supplemented with 20 ng/mL of Egf and Fgf‐2 (Sigma) and 2% B‐27 supplement (Gibco/Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Biodegradable Self‐Folding Polymer Films with Controlled Thermo‐Triggered Folding

Stroganov

Zakharchenko

Sperling

et al. 2014

Adv Funct Materials

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Self‐folding films are a unique kind of thin film. They are able to deform in response to a change in environmental conditions or internal stress and form complex 3D structures. They are very promising candidates for the design of bioscaffolds, which resemble different kinds of biological tissues. In this paper, a very simple and cheap approach for the fabrication of fully biodegradable and biocompatible self‐rolled tubes is reported. The tubes' folding can be triggered by temperature. A bilayer approach is used, where one component is active and another one is passive. The passive one can be any biocompatible, biodegradable, hydrophobic polymer. Gelatin is used as an active component: it allows the design of (i) self‐folding polymer films, which fold at room temperature (22 °C) and irreversibly unfold at 37 °C, and (ii) films, which are unfolded at room temperature (22 °C), but irreversibly fold at 37 °C. The possibilities of encapsulation of neural stem cells are also demonstrated using self‐folded tubes.

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Fetal mouse mesencephalic NPCs generate dopaminergic neurons from post-mitotic precursors and maintain long-term neural but not dopaminergic potential in vitro

Cited by 7 publications

References 51 publications

Dimensionality of Rolled-up Nanomembranes Controls Neural Stem Cell Migration Mechanism

Dimensionality of Rolled-up Nanomembranes Controls Neural Stem Cell Migration Mechanism

Epigenetic Activation of theFoxa2Gene Is Required for Maintaining the Potential of Neural Precursor Cells to Differentiate into Dopaminergic Neurons After Expansion

Biodegradable Self‐Folding Polymer Films with Controlled Thermo‐Triggered Folding

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