The nuclear receptor tailless promotes increase of neurogenesis after stroke
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE56397 | GEO | 2015/12/31
SECONDARY ACCESSION(S): PRJNA243132
REPOSITORIES: GEO
Similar Datasets
Project description:Tlx expression is upregulated after stroke, and stroke-induced neurogenesis is blocked when Tlx is inactivated. Tlx overexpression in NSCs leads to massive induction of neurogenesis via stroke, which leads to an improved motor function recovery. Four Tlx overexpressing mice, and 5 wild type mice as control. Technique repeat is done for one of the wild type mouse c1 to validate the quality of the data. Stroke are induced to all the mice by one side stratum ischemia.
2015-12-31 | E-GEOD-56397 | biostudies-arrayexpress
Project description:Tlx (nr2e1) is an orphan nuclear receptor that is highly expressed in proliferating neural stem cells (NSCs) in the adult mouse forebrain. The goal was to identify Tlx-regulated genes in this specific cell population. Two populations of Tlx-positive neural stem cells were isolated from 2-month-old male mice based on a LacZ marker that was knocked into the Tlx locus. The first population, Tlx(f/Z;CreER), contains a floxed allele of Tlx (f), the LacZ marker (Z), and a CreER fusion transgene. Addition of tamoxifen (4OH-tamoxifen) into this NSC population leads to Cre-mediated deletion of the floxed allele of Tlx. The second NSC population, Tlx(f/Z), does not contain a CreER transgene; thus it does not respond to tamoxifen treatment and was used as a control. Keywords: Nuclear receptor-dependent gene expression
2008-12-01 | GSE9981 | GEO
Project description:Tlx (nr2e1) is an orphan nuclear receptor that is highly expressed in proliferating neural stem cells (NSCs) in the adult mouse forebrain. The goal was to identify Tlx-regulated genes in this specific cell population. Two populations of Tlx-positive neural stem cells were isolated from 2-month-old male mice based on a LacZ marker that was knocked into the Tlx locus. The first population, Tlx(f/Z;CreER), contains a floxed allele of Tlx (f), the LacZ marker (Z), and a CreER fusion transgene. Addition of tamoxifen (4OH-tamoxifen) into this NSC population leads to Cre-mediated deletion of the floxed allele of Tlx. The second NSC population, Tlx(f/Z), does not contain a CreER transgene; thus it does not respond to tamoxifen treatment and was used as a control. Experiment Overall Design: Total RNA samples from two biological replicates were collected at 36 hr or at 60 hr after tamoxifen or vehicle treatment. Total of 16 samples were used to analyze the global gene expression changes using Affymetrix chips.
2009-01-13 | E-GEOD-9981 | biostudies-arrayexpress
Project description:Although neurogenesis in the adult brain recapitulates processes that occur during embryonic development, adult neurogenesis exhibits distinct characteristics from its embryonic counterpart. However, the intrinsic mechanism underlying the differential regulation of neurogenesis between these two stages remains unclear. Herein, we show that the ablation of RNA-binding protein HuR in neural stem cells (NSCs) impairs adult, but not embryonic, neurogenesis. HuR is predominantly expressed in the cytoplasm of embryonic NSCs but translocates into the nucleus of adult NSCs. Transcriptomic analysis of HuR-deficient adult NSCs revealed that nuclear HuR primarily regulates alternative splicing of numerous premRNA transcripts, including focal adhesion kinase (FAK). HuR-deficient adult NSCs generate increased FAK mRNA isoforms with shorter 5’ UTRs, leading to enhanced FAK mRNA translation and hyperactivated FAK signaling, and inhibition of FAK ameliorates defective adult neurogenesis and impaired hippocampus-dependent learning in HuR-deficient mice. Taken together, these findings reveal novel mechanistic insights into the differential regulation of embryonic and adult neurogenesis through developmental cytoplasmic-to-nuclear translocation of HuR in NSCs.
2019-11-04 | GSE137323 | GEO
Project description:It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA-rearrangements in the human neocortex. We show here that neither is the case, using immunohistochemistry, transcriptome-, genome- and ploidy-analyses, and determination of nuclear bomb test-derived 14C-concentration in neuronal DNA. A large proportion of cortical neurons display DNA-fragmentation and DNA-repair short time after stroke, whereas neurons at chronic stages after stroke show DNA-integrity, demonstrating the relevance of an intact genome for survival. Analyze of potential fusion transcripts in 13 samples, seven cortical ischemic stroke tissue and six control cortex, by deep sequencing using Illumina HiSeq 2000
2014-03-28 | E-GEOD-56267 | biostudies-arrayexpress
Project description:Neural stem cells (NSCs) generating new neurons are restricted to few niches in the adult mammalian brain, while the remainder rather promotes gliogenesis. Here we take advantage of the spatial separation of an NSC niche (the subependymal zone) and the region to where the newly generated neurons migrate and integrate (the olfactory bulb). Using state-of-the-art mass spectrometry we present a comprehensive proteomic characterization of these niches compared to a region of the normal brain parenchyma (cerebral cortex) that is not contusive to neurogenesis and new neuron integration. We find unique compositions of regulatory ECM components in the neurogenic niche, with quiescent NSCs as a main source of their local ECM, including the multi-functional enzyme transglutaminase 2 that we identify as crucial for neurogenesis. Atomic force microscopy further corroborates indications from the proteome that neurogenic niches are significantly stiffer than the non-neurogenic parenchyma, highlighting the unique properties of these special niches.
2020-01-27 | PXD016632 | Pride
Project description:Relative H3K27me3 enrichment, assessed by ChIP-on-chip, in two TLX positive and two TLX negative T Acute Lymphoblastique Leukemia (T-ALL) samples. Acute lymphoblastic leukemias (ALLs) are characterized by multi-step oncogenic processes leading to cell differentiation arrest and proliferation. Specific abrogation of maturation blockage constitutes a promising therapeutic option in cancer, which requires precise understanding of the underlying molecular mechanisms. We show that the cortical thymic maturation arrest in T-lineage ALL that over-express TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of the T cell receptor (TCR) alpha enhanceosome activity and blocked TCR-Jalpha rearrangement. TLX1/TLX3 abrogation or enforced TCRalpha/beta expression leads to TCRalpha rearrangement and apoptosis. Importantly, the auto-extinction of clones carrying TCRalpha-driven TLX1 expression supports TLX 'addiction' in TLX-positive leukemias and provides further rationale for targeted therapy based on disruption of TLX1/TLX3.
2012-07-17 | E-MEXP-3527 | biostudies-arrayexpress
Project description:Mutations in the JMJD3 (KDM6B) chromatin regulator are causally associated with autism spectrum disorder and syndromic intellectual disability, but the neurodevelopmental roles of this histone 3 lysine 27 (H3K27) demethylase are poorly understood. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) generate new granule neurons throughout life, and deficits in DG neurogenesis are associated with cognitive and behavioral problems. Here we show that Jmjd3 is required for the establishment of adult neurogenesis in the mouse DG. Conditional deletion of Jmjd3 in embryonic DG precursors results in an adult hippocampus that is essentially devoid of NSCs. While early postnatal mice with Jmjd3-deletion have near normal numbers of DG NSCs, at later stages, Jmjd3-deleted NSCs fail to propagate normally. In addition to the loss of NSCs during postnatal development, neurogenesis from Jmjd3-deleted NSCs is impaired, corresponding to defective neurogenic gene expression. Without Jmjd3, NeuroD2 and Bcl11b(Ctip2) are not properly expressed and exhibit increased levels of H3K27me3, underscoring the role of Jmjd3 in the regulation of transcription for neuronal differentiation. Thus, these data indicate that Jmjd3 plays dual roles in postnatal DG neurogenesis, being critical for the establishment of the NSC pool as well as the differentiation of young DG granule neurons. More broadly, our results suggest a neurodevelopmental link between JMJD3 mutations and hippocampal dysfunction, providing new insights into how mutations in chromatin regulators may contribute to learning disorders.
2021-04-01 | GSE73706 | GEO
Project description:we provide evidence that Med23 is involved in the regulation of adult hippocampal neurogenesis in mouse. Med23-deficient NSCs in the SGZ display faster self-renewal activity possibly by reducing cell cycle length, but neuroblasts, immature and mature new-born neurons are reduced.
2020-06-10 | GSE152113 | GEO
Project description:The epigenetic mechanisms that enable lifelong neurogenesis from neural stem cells (NSCs) in the adult mammalian brain are poorly understood. Here we show that JMJD3, a histone H3-lysine 27 (H3K27) demethylase, acts as a critical activator of neurogenesis. 3 biological replicates of JMJD3 null (P9 UBC-Cre/ERT2;Jmjd3F/F) and 3 biological replicates of littermate controls were used to analyze the effect of JMJD3 deletion on gene expression.
2014-07-30 | E-GEOD-59888 | biostudies-arrayexpress