title: RNA-seq of the aging brain in the short-lived fish N. furzeri - conserved pathways and novel genes associated with neurogenesis.
abstract: The brains of teleost fish show extensive adult neurogenesis and neuronal regeneration. The patterns of gene regulation during fish brain aging are unknown. The short-lived teleost fish Nothobranchius furzeri shows markers of brain aging including reduced learning performances, gliosis, and reduced adult neurogenesis. We used RNA-seq to quantify genome-wide transcript regulation and sampled five different time points to characterize whole-genome transcript regulation during brain aging of N. furzeri. Comparison with human datasets revealed conserved up-regulation of ribosome, lysosome, and complement activation and conserved down-regulation of synapse, mitochondrion, proteasome, and spliceosome. Down-regulated genes differ in their temporal profiles: neurogenesis and extracellular matrix genes showed rapid decay, synaptic and axonal genes a progressive decay. A substantial proportion of differentially expressed genes (~40%) showed inversion of their temporal profiles in the last time point: spliceosome and proteasome showed initial down-regulation and stress-response genes initial up-regulation. Extensive regulation was detected for chromatin remodelers of the DNMT and CBX families as well as members of the polycomb complex and was mirrored by an up-regulation of the H3K27me3 epigenetic mark. Network analysis showed extensive coregulation of cell cycle/DNA synthesis genes with the uncharacterized zinc-finger protein ZNF367 as central hub. In situ hybridization showed that ZNF367 is expressed in neuronal stem cell niches of both embryonic zebrafish and adult N. furzeri. Other genes down-regulated with age, not previously associated with adult neurogenesis and with similar patterns of expression are AGR2, DNMT3A, KRCP, MEX3A, SCML4, and CBX1. CBX7, on the other hand, was up-regulated with age.
authors: Leibniz Institute for Age Research - Fritz Lipmann Institute e.V. (FLI), Jena, Germany.
authors: Mario
authors: M
authors: Baumgart
authors: Marco
authors: M
authors: Groth
authors: Steffen
authors: S
authors: Priebe
authors: Aurora
authors: A
authors: Savino
authors: Giovanna
authors: G
authors: Testa
authors: Andreas
authors: A
authors: Dix
authors: Roberto
authors: R
authors: Ripa
authors: Francesco
authors: F
authors: Spallotta
authors: Carlo
authors: C
authors: Gaetano
authors: Michela
authors: M
authors: Ori
authors: Eva
authors: E
authors: Terzibasi Tozzini
authors: Reinhard
authors: R
authors: Guthke
authors: Matthias
authors: M
authors: Platzer
authors: Alessandro
authors: A
authors: Cellerino
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000090266:Chromobox Protein Homolog 5; D017124:Conserved Sequence; D003532:Cyprinodontiformes / Q000235:genetics*; D057890:Epigenomics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D023421:Models, Animal; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D059467:Transcriptome
chemical_list: C000715593:CBX1 protein, human; D000090266:Chromobox Protein Homolog 5; D012313:RNA
keywords: animal model; brain aging; epigenetics; gene expression; neural stem cells; neurogenesis; teleost; transcriptomics