miR-17~92 exerts stage-specific effects in adult V-SVZ neural stem cell lineages

Mapping Intimacies ◽

10.1101/2021.07.28.454109 ◽

2021 ◽

Author(s):

Fabrizio Favaloro ◽

Annina DeLeo ◽

Ana Delgado ◽

Fiona Doetsch

Keyword(s):

Stem Cell ◽

Neural Stem Cell ◽

Oligodendrocyte Progenitor Cells ◽

Dependent Manner ◽

Cell Lineages ◽

Conditional Deletion ◽

Specific Effects ◽

Cell Type Specific

In the adult mouse brain, neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ) generate neurons and glia throughout life. microRNAs are important regulators of cell states, frequently acting in a stage- or context-dependent manner. Here, miRNA profiling of FACS-purified populations identified miR-17~92 as highly upregulated in activated NSCs and transit amplifying cells (TACs) in comparison to quiescent NSCs. Conditional deletion of miR-17~92 in NSCs reduced stem cell proliferation both in vitro and in vivo. In contrast, in TACs, miR-17~92 deletion caused a selective shift from neurogenic DLX2+ TACs towards oligodendrogenic OLIG2+ TACs, resulting in increased oligodendrogenesis to the corpus callosum. miR-17~92 deletion also decreased proliferation and maturation of intraventricular oligodendrocyte progenitor cells. Together, these findings reveal stage- and cell-type- specific functions of the miR-17~92 cluster within adult V-SVZ neural stem cell lineages.

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Gender-specific effects of transthyretin on neural stem cell fate in the subventricular zone of the adult mouse

Scientific Reports ◽

10.1038/s41598-019-56156-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Pieter Vancamp ◽

Jean-David Gothié ◽

Cristina Luongo ◽

Anthony Sébillot ◽

Karine Le Blay ◽

...

Keyword(s):

Stem Cell ◽

Choroid Plexus ◽

Cell Fate ◽

Neural Stem Cell ◽

Subventricular Zone ◽

Mrna Levels ◽

Specific Effects ◽

Gender Specific

AbstractChoroid plexus epithelial cells produce and secrete transthyretin (TTR). TTR binds and distributes thyroid hormone (TH) to brain cells via the cerebrospinal fluid. The adult murine subventricular zone (SVZ) is in close proximity to the choroid plexus. In the SVZ, TH determines neural stem cell (NSC) fate towards a neuronal or a glial cell. We investigated whether the loss of TTR also disrupted NSC fate choice. Our results show a decreased neurogenic versus oligodendrogenic balance in the lateroventral SVZ of Ttr knockout mice. This balance was also decreased in the dorsal SVZ, but only in Ttr knockout male mice, concomitant with an increased oligodendrocyte precursor density in the corpus callosum. Quantitative RTqPCR analysis following FACS-dissected SVZs, or marked-coupled microbeads sorting of in vitro neurospheres, showed elevated Ttr mRNA levels in neuronal cells, as compared to uncommitted precursor and glial cells. However, TTR protein was undetectable in vivo using immunostaining, and this despite the presence of Ttr mRNA-expressing SVZ cells. Altogether, our data demonstrate that TTR is an important factor in SVZ neuro- and oligodendrogenesis. They also reveal important gender-specific differences and spatial heterogeneity, providing new avenues for stimulating endogenous repair in neurodegenerative diseases.

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Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽

10.3390/cells10040730 ◽

2021 ◽

Vol 10 (4) ◽

pp. 730

Author(s):

Biji Mathew ◽

Leianne A. Torres ◽

Lorea Gamboa Gamboa Acha ◽

Sophie Tran ◽

Alice Liu ◽

...

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Extracellular Vesicles ◽

Time Course ◽

Ganglion Cells ◽

Ex Vivo ◽

Dependent Manner ◽

Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

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Multifunctional silica-coated iron oxide nanoparticles: a facile four-in-one system for in situ study of neural stem cell harvesting

Faraday Discussions ◽

10.1039/c4fd00132j ◽

2014 ◽

Vol 175 ◽

pp. 13-26 ◽

Cited By ~ 15

Author(s):

Yung-Kang Peng ◽

Cathy N. P. Lui ◽

Tsen-Hsuan Lin ◽

Chen Chang ◽

Pi-Tai Chou ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Iron Oxide ◽

Magnetic Resonance ◽

Neural Stem Cells ◽

Neural Stem Cell ◽

Cell Therapies ◽

Bimodal Imaging

Neural stem cells (NSCs), which generate the main phenotypes of the nervous system, are multipotent cells and are able to differentiate into multiple cell types via external stimuli from the environment. The extraction, modification and re-application of NSCs have thus attracted much attention and raised hopes for novel neural stem cell therapies and regenerative medicine. However, few studies have successfully identified the distribution of NSCs in a live brain and monitored the corresponding extraction processes both in vitro and in vivo. To address those difficulties, in this study multi-functional uniform nanoparticles comprising an iron oxide core and a functionalized silica shell (Fe3O4@SiO2(FITC)-CD133, FITC: a green emissive dye, CD133: anti-CD133 antibody) have been strategically designed and synthesized for use as probe nanocomposites that provide four-in-one functionality, i.e., magnetic agitation, dual imaging (both magnetic resonance and optical) and specific targeting. It is shown that these newly synthesized Fe3O4@SiO2(FITC)-CD133 particles have clearly demonstrated their versatility in various applications. (1) The magnetic core enables magnetic cell collection and T2 magnetic resonance imaging. (2) The fluorescent FITC embedded in the silica framework enables optical imaging. (3) CD133 anchored on the outermost surface is demonstrated to be capable of targeting neural stem cells for cell collection and bimodal imaging.

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Protocadherin 11 X Regulates Differentiation and Proliferation of Neural Stem Cell In Vitro and In Vivo

Journal of Molecular Neuroscience ◽

10.1007/s12031-014-0275-x ◽

2014 ◽

Vol 54 (2) ◽

pp. 199-210 ◽

Cited By ~ 12

Author(s):

Peng Zhang ◽

Cuiying Wu ◽

Ning Liu ◽

Lijun Niu ◽

Zhongjie Yan ◽

...

Keyword(s):

Stem Cell ◽

Neural Stem Cell ◽

Differentiation And Proliferation

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Wnt/beta-catenin signalling is dispensable for adult neural stem cell homeostasis and activation

Development ◽

10.1242/dev.199629 ◽

2021 ◽

Author(s):

Sophie H. L. Austin ◽

Rut Gabarró-Solanas ◽

Piero Rigo ◽

Oana Paun ◽

Lachlan Harris ◽

...

Keyword(s):

Stem Cell ◽

In Vitro Models ◽

Beta Catenin ◽

Dependent Manner ◽

Direct Role ◽

Adult Nscs ◽

Hippocampal Networks ◽

Dose Dependent

Adult mouse hippocampal neural stem cells (NSCs) generate new neurons that integrate into existing hippocampal networks and modulate mood and memory. These NSCs are largely quiescent and are stimulated by niche signals to activate and produce neurons. Wnt/β-catenin signalling acts at different steps along the hippocampal neurogenic lineage, but whether it has a direct role in the regulation of NSCs remains unclear. Here we used Wnt/β-catenin reporters and transcriptomic data from in vivo and in vitro models to show that adult NSCs respond to Wnt/β-catenin signalling. Wnt/β-catenin stimulation instructed neuronal differentiation of NSCs in an active state and promoted the activation or differentiation of quiescent NSCs in a dose-dependent manner. However, we found that deletion of β-catenin in NSCs did not affect their activation or maintenance of their stem cell characteristics. Together, our results indicate that whilst NSCs do respond to Wnt/β-catenin stimulation in a dose-dependent and state-specific manner, Wnt/β-catenin signalling is not cell-autonomously required to maintain NSC homeostasis, which reconciles some of the contradictions in the literature as to the role of Wnt/β-catenin signalling in adult hippocampal NSCs.

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Wnt/beta-catenin signalling is dispensable for adult neural stem cell homeostasis and activation

10.1101/2020.12.29.424694 ◽

2020 ◽

Author(s):

Sophie H. L. Austin ◽

Lachlan Harris ◽

Oana Paun ◽

Piero Rigo ◽

François Guillemot ◽

...

Keyword(s):

Stem Cell ◽

Beta Catenin ◽

Dependent Manner ◽

Direct Role ◽

Adult Nscs ◽

Hippocampal Networks ◽

Dose Dependent

AbstractAdult mouse hippocampal neural stem cells (NSCs) generate new neurons that integrate into existing hippocampal networks and modulate mood and memory. These NSCs are largely quiescent and are stimulated by niche signals to activate and produce neurons. Wnt/β-catenin signalling acts at different steps along the hippocampal neurogenic lineage and has been shown to promote the proliferation of intermediate progenitor cells. However, whether it has a direct role in the regulation of NSCs still remains unclear. Here we used Wnt/β-catenin reporters and transcriptomic data from in vivo and in vitro models to show that both active and quiescent adult NSCs respond to Wnt/β-catenin signalling. Wnt/β-catenin stimulation instructed neuronal differentiation of active NSCs and promoted the activation or differentiation of quiescent NSCs in a dose-dependent manner. However, we found that inhibiting NSCs response to Wnt, by conditionally deleting β-catenin, did not affect their activation or maintenance of their stem cell characteristics. Together, our results indicate that whilst NSCs do respond to Wnt/β-catenin stimulation in a dose-dependent and state-specific manner, Wnt/β-catenin signalling is not cell-autonomously required to maintain NSC homeostasis, which could reconcile some of the contradictions in the literature as to the role of Wnt/β-catenin signalling in adult hippocampal NSCs.

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