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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Phylogenetic fate mapping
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Phylogenetic fate mapping

机译：系统发生命运映射

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摘要

Cell fate maps describe how the sequence of cell division, migration, and apoptosis transform a zygote into an adult. Yet, it is only in Caenorhabditis elegans where microscopic observation of each cell division has allowed for construction of a complete fate map. More complex, and opaque, animals prove less yielding. DNA replication, however, generates somatic mutations. Consequently, multicellular organisms comprise mosaics where most cells acquire unique genomes that are potentially capable of delineating their ancestry. Here we take a phylogenetic approach to passively retrace embryonic relationships by deducing the order in which mutations have arisen during development. We show that polyguanine repeat DNA sequences are particularly useful genetic markers, because they frequently change length during mitosis. To demonstrate feasibility, we phylogenetically reconstruct the lineage of cultured mouse NIH 3T3 cells based on mutations affecting the length of polyguanine markers. We then employ whole genome amplification to genotype polyguanine markers in single cells taken from a mouse and use phylogenetics to infer the developmental relationships of the sampled tissues. The result is consistent with the present understanding of embryogenesis and demonstrates the large scale potential of this method for producing a complete mammalian cell fate at the resolution of a single cell.
机译：细胞命运图描述了细胞分裂，迁移和凋亡的序列如何将合子转化为成年个体。然而，只有在秀丽隐杆线虫中，对每个细胞分裂的显微镜观察才可以构建完整的命运图。动物越复杂，越不透明，其产量就越低。但是，DNA复制会产生体细胞突变。因此，多细胞生物包含镶嵌体，其中大多数细胞获得了独特的基因组，这些基因组有可能描绘其祖先。在这里，我们采用系统发育方法，通过推导在发育过程中出现突变的顺序来被动地追溯胚胎关系。我们显示，聚鸟嘌呤重复DNA序列是特别有用的遗传标记，因为它们在有丝分裂期间经常改变长度。为了证明可行性，我们基于影响多鸟嘌呤标记长度的突变在系统发育上重建了培养的小鼠NIH 3T3细胞的谱系。然后，我们采用全基因组扩增来对小鼠单细胞中的基因型多鸟嘌呤标记进行基因型分析，并使用系统发育学来推断所采样组织的发育关系。结果与目前对胚胎发生的理解是一致的，并证明了该方法在单个细胞的分辨率下产生完整的哺乳动物细胞命运的大规模潜力。

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