RNA‐seq of the aging brain in the short‐lived fish N. furzeri – conserved pathways and novel genes associated with neurogenesis

Aging Cell

Mario Baumgart⁴  Marco Groth⁴  Steffen Priebe³  Aurora Savino¹  Giovanna Testa¹  Andreas Dix³  Roberto Ripa¹  Francesco Spallotta²  Carlo Gaetano²  Michela Ori⁵  Eva Terzibasi Tozzini¹  Reinhard Guthke³  Matthias Platzer⁴ 

[1] Laboratory of NeuroBiology, Scuola Normale Superiore, University of Pisa, Pisa, Italy;Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany;Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute e.V. (HKI), Jena, Germany;Leibniz Institute for Age Research - Fritz Lipmann Institute e.V. (FLI), Jena, Germany;Department of Biology, University of Pisa, Pisa, Italy

关键词: animal model;    brain aging;    epigenetics;    gene expression;    neural stem cells;    neurogenesis;    teleost;    transcriptomics;   

DOI  :  10.1111/acel.12257

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2014 The Authors. Aging cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.