Life-long persistence of nuclear RNAs in the mouse brain [NPCs]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE248099 | GEO | 2024/04/04
REPOSITORIES: GEO
Similar Datasets
Project description:Genomic DNA residing in the nuclei of mammalian neurons can be as old as the organism itself. The life span of non-coding nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. Here, we report the identification and characterization of nuclear RNAs that do not turn over for at least two years in the adult mouse brain. These long-lived RNAs (LL-RNA) are stably retained in nuclei in a neural cell type-specific manner and are required for the maintenance of heterochromatin. Thus, the remarkable life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information but also the extreme stability of RNA for the functional organization of chromatin.
2024-04-04 | GSE248100 | GEO
Project description:Dietary restriction (DR) is the best-characterized intervention for slowing aging, and reduced signaling through the target of rapamycin (TOR) kinase is believed to be one of the key mechanisms by which DR extends life span in organisms from yeast to mammals. Here we describe a role for nuclear sequestration of tRNA in yeast replicative life span (RLS) extension from DR. DR causes the nuclear tRNA exporter Los1 to become depleted from the nucleus by a mechanism that requires the DNA damage response factor Rad53, and deletion of LOS1 or overexpression of RAD53 is sufficient to extend RLS. We further report that activation of the nitrogen responsive transcription factor Gln3 is the primary mechanism by which DR extends RLS. Gln3 is activated by both branches of the DR response and is required for life span extension. Overexpression of Gln3 extends RLS by approximately 50%.
2015-02-03 | GSE37241 | GEO
Project description:Expression data from four different lifespan-extending conditions: dietary restriction in two different genetic backgrounds (canton-s and a yw, w1118 combination), sir2 overexpression and p53 knockdown (+/-). Comparison of significantly over and under-expressed genes reveals a signature for dietary restriction and lifespan extension. Abstract A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway.
2011-01-20 | GSE26726 | GEO
Project description:Dietary restriction (DR) is the best-characterized intervention for slowing aging, and reduced signaling through the target of rapamycin (TOR) kinase is believed to be one of the key mechanisms by which DR extends life span in organisms from yeast to mammals. Here we describe a role for nuclear sequestration of tRNA in yeast replicative life span (RLS) extension from DR. DR causes the nuclear tRNA exporter Los1 to become depleted from the nucleus by a mechanism that requires the DNA damage response factor Rad53, and deletion of LOS1 or overexpression of RAD53 is sufficient to extend RLS. We further report that activation of the nitrogen responsive transcription factor Gln3 is the primary mechanism by which DR extends RLS. Gln3 is activated by both branches of the DR response and is required for life span extension. Overexpression of Gln3 extends RLS by approximately 50%. In order to identify potential factors acting to modulate longevity downstream of Los1, we used microarray analysis to compare the gene expression profiles of wild type and LOS1 knockout cells under non-restricted conditions cultured overnight prior to RNA isolation.
2015-02-03 | E-GEOD-37241 | biostudies-arrayexpress
Project description:Expression data from four different lifespan-extending conditions: dietary restriction in two different genetic backgrounds (canton-s and a yw, w1118 combination), sir2 overexpression and p53 knockdown (+/-). Comparison of significantly over and under-expressed genes reveals a signature for dietary restriction and lifespan extension. Abstract A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway. 42 samples were used in the analysis. Sir2 overexpression flies and the yw, w1118 background DR flies had the same control. Flies were collected at ages 10 and 40 days. Tissue is whole body females.
2011-01-20 | E-GEOD-26726 | biostudies-arrayexpress
Project description:The mammalian adult brain contains two neural stem and precursor (NPC) niches: subventricular zone [SVZ] lining the lateral ventricles and subgranular zone [SGZ] in the hippocampus. From these SVZ NPCs represent the largest NPC pool. Notably, while SGZ NPCs typically only produce neurons and astrocytes, SVZ NPCs produce neurons, astrocytes and oligodendrocytes throughout life. Of particular importance is the generation and replacement of oligodendrocytes, the only myelinating cells of the central nervous system (CNS). SVZ NPCs contribute to myelination by regenerating oligodendrocyte precursor cell (OPC) pool and by differentiating into oligodendrocytes in the developing and demyelinated brain. The neurosphere assay has been widely adopted by the scientific community to facilitate the study of NPCs in vitro. Here, we present a streamlined protocol for culturing postnatal and adult SVZ NPCs and OPCs from primary neurosphere cells. We characterize the purity and differentiation potential as well as provide RNA-sequencing profiles of postnatal SVZ NPCs, postnatal SVZ OPCs and adult SVZ NPCs. We show that primary neurospheres cells generated from postnatal and adult SVZ differentiate into neurons, astrocytes and oligodendrocytes concurrently and at comparable levels. SVZ OPCs are generated by subjecting primary neurosphere cells to OPC growth factors fibroblast growth factor (FGF) and platelet-derived growth factor-AA (PDGF-AA). We further show SVZ OPCs can differentiate into oligodendrocytes in the absence and presence of thyroid hormone T3. Transcriptomic analysis confirmed the identities of each cell population and revealed novel immune and signalling pathways expressed in an age and cell type specific manner.
2022-12-19 | GSE217507 | GEO
Project description:Cell type specific gene expression profiling was performed with adult Drosophila photoreceptors. Two genotypes were compared: ninaE wild type control and ninaEG69D/+ mutants that have chronic endoplasmic reticulum stress. To specifically isolate RNAs from these cell types, we drove nuclear envelope-localized EGFP::Msp300KASH expression with the photoreceptor specific Rh1-Gal4 driver. Anti-GFP beads were used to isolate the nuclei from those adult fly photoreceptor cells. Novaseq was used to perform RNA-seq.
2021-10-02 | GSE185134 | GEO
Project description:In this study, proteomic analysis on ZIKV-infected primary human fetal neural progenitor cells (NPCs) revealed that virus infection altered levels of cellular proteins involved in NPC proliferation, differentiation and migration.
2018-06-25 | PXD009343 | Pride
Project description:The significant increase in the human life-span during the last century confronts us with great medical challenges. To answer them, one must understand and control the mechanisms that determine healthy ageing. The highly conserved sirtuin deacetylases were shown to regulate life-span in lower organisms. Yet, the role of mammalian sirtuins, SIRT1 to 7, in regulating life-span is currently unclear. Here, we show that in SIRT6 transgenic mice (Sirt6-tg), the males but not the females, have a significant increase in life-span. Gene expression analysis revealed significant differences for male Sirt6-tg in comparison to male wild-type mice. Transgenic males display lower serum IGF-1 levels, increased levels of IGFBP-1 and altered phosphorylation levels of major components of the IGF-1 pathway, a key factor in the regulation of life-span. This study is the first to show regulation of mammalian life-span by a sirtuin family member, and has important therapeutic implications for age-related diseases.
2012-04-01 | E-MTAB-871 | biostudies-arrayexpress
Project description:Comparison of wild type and heterozygote and homozygote chico mutants ( Clancy, et al. Extension of Life-Span by Loss of CHICO, a Drosophila Insulin Receptor Substrate Protein. Science 292 (5514), 104.) on Affymetrix Drosophila2 GeneChip. The flies (Drosophila melanogaster) are 7 day old adult females.
2007-06-06 | E-MEXP-1099 | biostudies-arrayexpress