The Complete Genome Sequences, Unique Mutational Spectra, and Developmental Potency of Adult Neurons Revealed by Cloning.
The Complete Genome Sequences, Unique Mutational Spectra, and Developmental Potency of Adult Neurons Revealed by Cloning.
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DOI：
10.1016/j.neuron.2016.02.004
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发表时间：
2016-03-16
期刊：
影响因子：
16.2
通讯作者：
Baldwin KK
中科院分区：
文献类型：
--
作者：
Hazen JL;Faust GG;Rodriguez AR;Ferguson WC;Shumilina S;Clark RA;Boland MJ;Martin G;Chubukov P;Tsunemoto RK;Torkamani A;Kupriyanov S;Hall IM;Baldwin KK
神经元的体细胞突变与神经系统疾病有关，并与细胞类型多样化有关。然而，神经元中基因组突变的起源、程度和模式仍然未知。我们建立了一种克隆扩增成年小鼠神经元基因组的核转移方法，用于全基因组测序。全面的突变检测和独立验证表明，单个神经元含有来自所有类别的约100个独特突变，但缺乏经常性重排。大多数神经元含有至少一个基因破坏突变和罕见的（0-2）移动的元件插入。神经元突变的频率和基因偏好与其他谱系不同，可能是由于有丝分裂后突变的新机制。从几个神经元中克隆了可生育小鼠，建立了突变的成年神经元基因组与多能性和发育重编程的相容性。
Somatic mutation in neurons is linked to neurologic disease and implicated in cell type diversification. However, the origin, extent and patterns of genomic mutation in neurons remain unknown. We established a nuclear transfer method to clonally amplify the genomes of neurons from adult mice for whole genome sequencing. Comprehensive mutation detection and independent validation revealed that individual neurons harbor ~100 unique mutations from all classes, but lack recurrent rearrangements. Most neurons contain at least one gene disrupting mutation and rare (0-2) mobile element insertions. The frequency and gene bias of neuronal mutations differs from other lineages, potentially due to novel mechanisms governing post-mitotic mutation. Fertile mice were cloned from several neurons, establishing the compatibility of mutated adult neuronal genomes with reprogramming to pluripotency and development.