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Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis

机译:妊娠前和神经发生中人类细胞的不同突变率和机制

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摘要

Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks postconception) using clonal cell populations. We detected 200 to 400 single-nucleotide variations (SNVs) per cell. SNV patterns resembled those found in cancer cell genomes, indicating a role of background mutagenesis in cancer. SNVs with a frequency of 2% in brain were also present in the spleen, revealing a pregastrulation origin. We reconstructed cell lineages for the first five postzygotic cleavages and calculated a mutation rate of similar to 1.3 mutations per division per cell. Later in development, during neurogenesis, the mutation spectrum shifted toward oxidative damage, and the mutation rate increased. Both neurogenesis and early embryogenesis exhibit substantially more mutagenesis than adulthood.
机译:人脑中的体细胞镶嵌可能会改变单个神经元的功能。我们使用克隆细胞群分析了三个人类胎儿(受孕后15至21周)前脑的单细胞基因组。我们每个细胞检测到200到400个单核苷酸变异(SNV)。 SNV模式类似于在癌细胞基因组中发现的模式,表明背景诱变在癌症中的作用。脾脏中也有SNV出现在大脑中的频率> 2%,这表明了妊娠前的起源。我们重建了前五个后合子裂解的细胞谱系,并计算出每个细胞每分裂1.3个突变的突变率。在后来的发展中,在神经发生过程中,突变谱向氧化损伤转移,并且突变率增加。与成年相比,神经发生和早期胚胎发生均表现出更多的诱变作用。

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  • 来源
    《Science》 |2018年第6375期|550-555|共6页
  • 作者单位

    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA;

    Yale Univ, Child Study Ctr, New Haven, CT 06520 USA;

    Yale Univ, Child Study Ctr, New Haven, CT 06520 USA;

    Stanford Univ, Dept Psychiat, Palo Alto, CA 94305 USA;

    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA;

    Yale Univ, Dept Neurosci, New Haven, CT 06520 USA;

    Yale Univ, Dept Neurosci, New Haven, CT 06520 USA;

    Stanford Univ, Dept Psychiat, Palo Alto, CA 94305 USA;

    New York Genome Ctr, New York, NY 10013 USA;

    New York Genome Ctr, New York, NY 10013 USA;

    New York Genome Ctr, New York, NY 10013 USA;

    Yale Univ, Dept Neurosci, New Haven, CT 06520 USA;

    Stanford Univ, Dept Psychiat, Palo Alto, CA 94305 USA;

    Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA;

    Yale Univ, Child Study Ctr, New Haven, CT 06520 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 入库时间 2022-08-18 02:51:01

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