Project description:This SuperSeries is composed of the following subset Series: GSE22473: Murine postnatal subventricular zone (SVZ) neural stem cells (NSCs): Wild-type (WT) vs. Dnmt3a-null (KO) GSE22474: Genome-wide location analysis of Dnmt3a-mediated epigenetic regulation in murine postnatal subventricular zone (SVZ) neural stem cells (NSCs) [Agilent] GSE22475: Genome-wide location analysis of Dnmt3a-mediated epigenetic regulation in murine postnatal subventricular zone (SVZ) neural stem cells (NSCs) [NimbleGen] Refer to individual Series
Project description:Microglia are the primary phagocytes in the central nervous system and are responsible for clearing dead cells generated during development or disease. The phagocytic process shapes the phenotype of the microglia, which affects the local environment. A unique population of microglia reside in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence this neurogenic niche is not well-understood. Here, we demonstrate that phagocytosis creates a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering the development of a neuroinflammatory phenotype, reminiscent of neurodegenerative and-age-associated microglia, that reduces neural precursor proliferation via elevated interleukin (IL)-1β signaling; inhibiton of IL-1 receptor rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to a phenotype that promotes neurogenesis in the developing V-SVZ. We performed RNAseq on MACS-sorted microglia from V-SVZ and Cortex of WT and Jedi-1 knockout P7 mice.
Project description:Purpose: Recent findings indicate a regulatory role of microglia on neurogenesis in the SVZ in health and disease. Microglia in the early postnatal SVZ are not fully maturated and may react differently than adult microglia to injury. We sought to investigate the impact of cortico-striatal neonatal HI injury on the microglial phenotype in the early postnatal SVZ. Results: In comparison to sham SVZ microglia, HI SVZ microglia upregulate both pro- and anti-inflammatory genes as well as neurotrophic genes. HI SVZ microglia do not adopt a M1 or M2 polarization state, but instead share commonly expressed genes with microglia in rodent models of neurodegenerative diseases.
Project description:Transcriptional profiling of subventricular zone (SVZ) progenitors comparing control healthy mice to mice induced to develop an autoimmune demyelination (EAE model). Goal was to unveil genes involved in demyelination-induced reactivity of SVZ progenitors.
Project description:The epigenetic mechanisms that enable specialized astrocytes to retain neurogenic competence throughout adult life are still poorly understood. Here we show that astrocytes that serve as neural stem cells (NSCs) in the adult mouse subventricular zone (SVZ) express the histone methyltransferase EZH2. This Polycomb repressive factor is required for neurogenesis independent of its role in SVZ NSC proliferation, as Ink4a/Arf-deficiency in Ezh2-deleted SVZ NSCs rescues cell proliferation, but neurogenesis remains defective. Olig2 is a direct target of EZH2, and repression of this bHLH transcription factor is critical for neuronal differentiation. Furthermore, Ezh2 prevents the inappropriate activation of genes that specify non-SVZ neuronal subtypes. In the human brain, SVZ cells including local astroglia also express EZH2, correlating with postnatal neurogenesis. Thus, EZH2 is an epigenetic regulator that distinguishes neurogenic SVZ astrocytes, orchestrating distinct and separable aspects of adult stem cell biology, which has important implications for regenerative medicine and oncogenesis. Examination of histone modifications (H3K27me3 and H3K4me3) in subventricular zone neural stem cells
Project description:Ischemic stroke is a serious medical condition that leads to the onset of neurological symptoms such as loss of motor and cognitive functions. Focal cerebral ischemia (FCI) occurs due to the interrupted blood supply to the site of injury, resulting in the demise of brain cells. The subventricular zone (SVZ) is a source of stem and progenitor cells (NS/PCs), which proliferate and differentiate in multiple cell types in order to substitute the injured tissue. We isolated cells from the SVZ and the adjacent striatum three days after middle cerebral artery occlusion (MCAO) in order to map cellular changes and NS/PCs plasticity in adult brain upon injury. Expression profiling of the isolated tissue at the single cell level enables the identification of cell population subtypes in the region and their characteristic gene expression.
Project description:Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. 16 Large White newborn female piglets were exposed to a tightly controlled hypoxic-ischemic insult using magnetic resonance spectroscopy (MRS) biomarkers. After hypoxia-ischemia (HI), piglets were randomized to: (i) no intervention (nâ=â8); (ii) RIPostC â with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (nâ=â8). Piglets in the remote post-conditioned group exhibited a reduction in white matter proton MRS lactate/N acetyl aspartate and increased whole brain phosphorus-31 MRS ATP over the 48âh after hypoxia-ischemia. Cell death (apoptosis) was reduced with RIPostC in the periventricular white matter, internal capsule and corpus callosum. There was also reduced microglial activation in corpus callosum and more surviving oligodendrocytes in corpus callosum and periventricular white matter. Our results demonstrate changes in the expression of 74 genes in the periventricular white matter 63 were down regulated and 11 were upregulated, that accompany the reductions in cell death and microglial activation seen following a remote post conditioning stimulus at a single 48h time point. (significance was calculated at p<0.05, one way ANOVA, Mann-Whitney unpaired, noe were found to be significant following a Benjamini-Hochberg FDR multipe testing correction). Many of these genes are thought to be important for the mediation of the neuroprotective effects of post-conditioning which suggests its genomic effects may persist for 48h. A full description of this work can be accessed at doi: 10.1177/0271678X15608862.
Project description:Comparison of gene expression of Ink4a/Arf-/- vs Bmi1-/-;Ink4a/Arf-/- subventricular zone (SVZ) derived mouse neural stem cells (NSC) on Laminin (LM) and Fibronectin (FN) substrates.
Project description:To analyze OTX2 function in adult choroid plexus, we performed several OTX2 co-immunoprecipitation (co-IP) experiments with mass spectrometry analysis to identify potential protein partners. We previously discovered that OTX2 protein also accumulates non-cell autonomously in subventricular zone (SVZ) and rostral migratory stream (RMS) astrocytes and in visual cortex (VCx) parvalbumin cells. The identification of alternate protein partners in cell-autonomous and non-cell-autonomous contexts would suggest OTX2 takes on specific roles after transferring between cells. In order to test this hypothesis, and to reinforce choroid plexus analysis, we also performed OTX2 co-IP on lysates from adult mouse SVZ, RMS and VCx.
