RNA-seq of the aging brain in the short-lived fish N. furzeri - conserved pathways and novel genes associated with neurogenesis.
RNA-seq of the aging brain in the short-lived fish N. furzeri - conserved pathways and novel genes associated with neurogenesis.
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DOI：
10.1111/acel.12257
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发表时间：
2014-12
期刊：
影响因子：
7.8
通讯作者：
Cellerino A
中科院分区：
文献类型：
--
作者：
Baumgart M;Groth M;Priebe S;Savino A;Testa G;Dix A;Ripa R;Spallotta F;Gaetano C;Ori M;Terzibasi Tozzini E;Guthke R;Platzer M;Cellerino A
硬骨鱼的大脑显示出广泛的成年神经发生和神经元再生。鱼脑老化过程中的基因调控模式尚不清楚。短寿命硬骨鱼Nothobranchius furzeri显示出大脑老化的标志，包括学习能力下降，神经胶质增生和成年神经发生减少。我们使用RNA-seq来量化全基因组转录调控，并在五个不同的时间点取样，以表征N. furzeri脑老化过程中的全基因组转录调控。与人类数据集的比较显示，保守的上调核糖体，溶酶体和补体激活和保守的下调突触，突触体，蛋白酶体和剪接体。下调基因的时间分布不同：神经发生和细胞外基质基因表现为快速衰减，突触和轴突基因表现为进行性衰减。相当比例的差异表达基因（约40%）在最后一个时间点显示其时间分布反转：剪接体和蛋白酶体显示初始下调和应激反应基因初始上调。检测到DNMT和CBX家族以及polycomb复合物成员的染色质重塑的广泛调节，并通过H3 K27 me 3表观遗传标记的上调来反映。网络分析表明，广泛的细胞周期/DNA合成基因的共同调控与未表征的锌指蛋白ZNF 367作为中央枢纽。原位杂交结果表明，ZNF 367在斑马鱼胚胎和成年体的神经干细胞中均有表达。其他随年龄下调的基因，以前与成人神经发生无关，具有相似的表达模式，是AGR 2，DNMT 3A，KRCP，MEX 3A，SCML 4和CBX 1。另一方面，CBX 7随着年龄的增长而上调。
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.
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影响因子：
9.8
作者：
David DC;Ollikainen N;Trinidad JC;Cary MP;Burlingame AL;Kenyon C
通讯作者：
Kenyon C
影响因子：
4.1
作者：
Blažek R;Polačik M;Reichard M
通讯作者：
Reichard M
影响因子：
25
作者：
Favaro, Rebecca;Valotta, Menella;Nicolis, Silvia K.
通讯作者：
Nicolis, Silvia K.
影响因子：
7.8
作者：
Jonker MJ;Melis JP;Kuiper RV;van der Hoeven TV;Wackers PFK;Robinson J;van der Horst GT;Dollé ME;Vijg J;Breit TM;Hoeijmakers JH;van Steeg H
通讯作者：
van Steeg H
人类大脑发育和衰老过程中广泛的剪接变化
影响因子：
9.9
作者：
Mazin, Pavel;Xiong, Jieyi;Khaitovich, Philipp
通讯作者：
Khaitovich, Philipp