Project description:Our aim in this study was to investigate the gene expression changes through pre-adult to adult, and adult to old age, in zebrafish brains. We isolated the neuronal cells and performed RNA sequencing in 3 months old, 6-8.5 months old, and 26-31 months old zebrafish brains. The cells were enriched in progenitor cell markers, which diminished throughout the aging process.
Project description:MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 233 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that function during aging in the human brain. 2 samples examined: Mouse brain from two young (5 months) and two old animals (24-25 months).
Project description:Zebrafish CNS-PNET tumors were generated by activating NRAS in oligoneural precursor cells. Gene expression in the zebrafish brain tumors and normal zebrafish brain was analyzed by RNA-seq.
Project description:The ATP-binding cassette subfamily B member 1 (ABCB1), encoding a multidrug transporter P-glycoprotein, plays a critical role in the efflux of xenobiotics in humans and is implicated in cancer resistance to chemotherapy—however, little information regarding Pgp at the zebrafish. In addition, to study the function of Pgp in the zebrafish brain in the aging process, we performed RNA-seq using brain tissue of WT and abcb4 knockout zebrafish at different ages, such as 2 months and 30 months.
Project description:Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.
Project description:Here we show that the aging of neural stem and progenitor cells (NSPCs) in the mouse brain is characterized by a decrease in the generation efficacy of proliferative NSPCs, rather than the changes in lineage specificity of NSPCs. We reveal that the downregulation of age-dependent genes in NSPCs drives cell aging by decreasing the population of actively proliferating NSPCs, while increasing the expression of quiescence markers. We find that epigenetic deregulation of MLL complex at promoters leads to transcriptional inactivation of age-dependent genes, highlighting the importance of the dynamic interaction between histone modifiers and gene regulatory elements in regulating transcriptional program of aging cells. Our study sheds light on the key intrinsic mechanisms driving stem cell aging through epigenetic regulators and identifies potential rejuvenation targets that could restore the function of aging stem cells.
Project description:In mouse, spermatogonial stem/progenitor cells are the progenitor cell which develop to mature sperms through a series of mitotic and meiotic divisions and differentiation. Gfra1 is an established surface marker for mouse spermatogonial stem/progenitor cells. In this study, we used a transcriptomic approach to investigate the effect of aging on Gfra1-positive and -negative populations of mouse male germ cells. Spermatogonial stem/progenitor cells were isolated from testes of mice at ages 6-day, 21-day, 60-day, and 8-months by magnetic assisted cell sorting (MACS) technique using Gfra1 marker. Transcriptomes among different ages and Gfra1 status were compared.
Project description:MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 233 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that function during aging in the human brain.
Project description:Meta analysis of transcriptome to reveal aging-related transcritionl alterations in zebrafish heart and provide candidate genes for development of model of premature cardiac aging