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Gene expression profiles of mouse embryonic neural stem/progenitor cells during astrocyte differentiation

ABSTRACT: We performed a microarray experiment to compare gene expression profiles of neural stem/progenitor cells (NS/PCs) with different culture conditions.

ORGANISM(S): Mus musculus

PROVIDER: GSE134208 | GEO | 2019/07/13

REPOSITORIES: GEO

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DNA methylome analysis identifies transcription factor-based epigenomic signatures of multi-lineage competence in neural stem/progenitor cells

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Gene expression profiles of mouse embryonic neural stem/progenitor cells during astrocyte differentiation

Project description:Gene expression profiles of mouse embryonic neural stem/progenitor cells during astrocyte differentiation

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Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptomes of neural stem/progenitor cells (NS/PCs) in control and prenatal valproic acid (VPA) exposed mice with or without voluntary exercise

Project description:Purpose: The goals of this study are to investigate the effect of prenatal VPA exposure on transcriptome profile of NS/PCs during development, and the effect of exercise on transcriptome profile of adult NS/PCs in prenatal VPA exposed mice. Methods: NS/PCs mRNA profiles of embryonic day15 (E15), postnatal day5 (P5) and 12-week-old (12w) contol mice and E15, P5, 12w with or without voluntary exercise prenatal VPA exposed mice were generated by deep sequencing, in triplicate, using Illumina Hiseq 2500. The sequence reads that passed quality filters were analyzed at the transcript isoform level with a method: TopHat/Bowtie2 followed by Cufflinks.NS/PCs were isolated from forebrain (E15), hippocampal dentate gyrus (P5 and 12w) of Nestin-EGFP mice. Results: Hierarchial clustering using eighteen samples (E15 Ctrl, E15 VPA, P5 Ctrl, P5 VPA, 12w Ctrl, 12w VPA, three samples each) identified three distinct clusters composed of NS/PCs derived from each developmental stage. Gene set enrichment analysis using transcriptome of E15 Ctrl and E15 VPA revealed a significant increase in the expression of neuron differentiation- and nervous system development-related genes in VPA compared with Ctrl. Gene ontology analysis of biological processes using differentially expressed genesin 12w VPA compared with 12w Ctrl revealed that expression levels of cell-migration-associated genes were altered. Voluntary running mostly amended both positively and negativly distorted gene expression in the 12w VPA compared with 12w Ctrl NS/PCs. The altered expression of cell migration-related genes was largely normalized by voluntary running.

2018-03-15 | GSE101239 | GEO

Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation.

Project description:Multipotent neural stem/progenitor cells (NSPCs) can be isolated from many regions of the adult central nervous system (CNS), yet neurogenesis is restricted to the hippocampus and subventricular zone in vivo. Identification of the molecular cues that modulate NSPC fate choice is a prerequisite for their therapeutic applications. Previously, we demonstrated that primary astrocytes isolated from regions with higher neuroplasticity, such as newborn and adult hippocampus and newborn spinal cord, promoted neuronal differentiation of adult NSPCs, whereas astrocytes isolated from the nonneurogenic region of the adult spinal cord inhibited neural differentiation. To identify the factors expressed by these astrocytes that could modulate NSPC differentiation, we performed gene expression profiling analysis using Affymetrix rat genome arrays. Our results demonstrated that these astrocytes had distinct gene expression profiles. We further tested the functional effects of candidate factors that were differentially expressed in neurogenesis-promoting and -inhibiting astrocytes using in vitro NSPC differentiation assays. Our results indicated that two interleukins, IL-1beta and IL-6, and a combination of factors that included these two interleukins could promote NSPC neuronal differentiation, whereas insulin-like growth factor binding protein 6 (IGFBP6) and decorin inhibited neuronal differentiation of adult NSPCs. Our results have provided further evidence to support the ongoing hypothesis that, in adult mammalian brains, astrocytes play critical roles in modulating NSPC differentiation. The finding that cytokines and chemokines expressed by astrocytes could promote NSPC neuronal differentiation may help us to understand how injuries induce neurogenesis in adult brains.

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ES, EC, NS, TS, Placenta and Neural induction (N2B27) comaprison

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Single cell RNA-seq analysis of feeder-free iPSC-derived gliogenic NS/PCs and neurogenic NS/PCs

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Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus.

Project description:The purpose of this study was to investigate the ability of astrocyte-derived factors to influence neural progenitor cell differentiation. We previously demonstrated that rat adult hippocampal progenitor cells (AHPCs) immunoreactive for the neuronal marker class III beta-tubulin (TUJ1) were significantly increased in the presence of astrocyte-derived soluble factors under noncontact coculture conditions. Using whole-cell patch-clamp analysis, we observed that the cocultured AHPCs displayed two prominent voltage-gated conductances, tetraethyl ammonium (TEA)-sensitive outward currents and fast transient inward currents. The outward and inward current densities of the cocultured AHPCs were approximately 2.5-fold and 1.7-fold greater, respectively, than those of cells cultured alone. These results suggest that astrocyte-derived soluble factors induce neuronal commitment of AHPCs. To investigate further the activity of a candidate neurogenic factor on AHPC differentiation, we cultured AHPCs in the presence or absence of purified rat recombinant interleukin-6 (IL-6). We also confirmed that the astrocytes used in this study produced IL-6 by ELISA and RT-qPCR. When AHPCs were cultured with IL-6 for 6-7 days, the TUJ1-immunoreactive AHPCs and the average length of TUJ1-immunoreactive neurites were significantly increased compared with the cells cultured without IL-6. Moreover, IL-6 increased the inward current density to an extent comparable to that of coculture with astrocytes, with no significant differences in the outward current density, apparent resting potential, or cell capacitance. These results suggest that astrocyte-derived IL-6 may facilitate AHPC neuronal differentiation. Our findings have important implications for understanding injury-induced neurogenesis and developing cell-based therapeutic strategies using neural progenitors.

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Expression data of neural progenitor cells differentiation from human embryonic stem cells

2014-09-03 | GSE61050 | GEO

Endothelial cells regulate astrocyte to neural progenitor cell trans-differentiation in a mouse model of stroke.

Project description:The concept of the neurovascular unit emphasizes the importance of cell-cell signaling between neural, glial, and vascular compartments. In neurogenesis, for example, brain endothelial cells play a key role by supplying trophic support to neural progenitors. Here, we describe a surprising phenomenon where brain endothelial cells may release trans-differentiation signals that convert astrocytes into neural progenitor cells in male mice after stroke. After oxygen-glucose deprivation, brain endothelial cells release microvesicles containing pro-neural factor Ascl1 that enter into astrocytes to induce their trans-differentiation into neural progenitors. In mouse models of focal cerebral ischemia, Ascl1 is upregulated in endothelium prior to astrocytic conversion into neural progenitor cells. Injecting brain endothelial-derived microvesicles amplifies the process of astrocyte trans-differentiation. Endothelial-specific overexpression of Ascl1 increases the local conversion of astrocytes into neural progenitors and improves behavioral recovery. Our findings describe an unexpected vascular-regulated mechanism of neuroplasticity that may open up therapeutic opportunities for improving outcomes after stroke.

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