Differential L1 regulation in pluripotent stem cells of humans and apes.
Differential L1 regulation in pluripotent stem cells of humans and apes.
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DOI：
10.1038/nature12686
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发表时间：
2013-11-28
期刊：
影响因子：
64.8
通讯作者：
Gage, Fred H.
中科院分区：
文献类型：
--
作者：
Marchetto, Maria C. N.;Narvaiza, Inigo;Denli, Ahmet M.;Benner, Christopher;Lazzarini, Thomas A.;Nathanson, Jason L.;Paquola, Apua C. M.;Desai, Keval N.;Herai, Roberto H.;Weitzman, Matthew D.;Yeo, Gene W.;Muotri, Alysson R.;Gage, Fred H.
识别人类和非人类灵长类动物（NHPs）之间的细胞和分子差异对于基本了解我们自己物种的进化和多样性至关重要。到目前为止，保存下来的组织一直是大多数人类、黑猩猩（Pan troglodytes）和倭黑猩猩（Pan paniscus）比较研究的主要来源。然而，这些组织样本不能公平地代表活细胞行为的独特特征，也不能接受基因操作。我们假设诱导多能干细胞（iPSCs）可能是一种独特的生物资源，可以阐明人类和NHPs之间的相关表型差异，这些差异可能具有潜在的适应和物种形成价值。在这里，我们描述了来自黑猩猩和倭黑猩猩的iPSCs的产生和初始特征，作为探索促成类人猿进化的因素的新工具。比较人类和NHP iPSCs的基因表达分析发现，长穿插核元件-1 （LINE-1或L1）转座子的调控存在差异。作为哺乳动物进化过程中的一种改变力量，L1元件是在灵长类动物进化过程中保持活跃的反转录转座子。NHP iPSCs中L1限制因子APOBEC3B （A3B）和PIWIL2水平的降低与L1迁移率和内源性L1 mRNA水平的升高相关。此外，操纵iPSCs中A3B和PIWIL2水平的结果支持这些蛋白水平与L1反转录转位之间的因果反比关系。最后，我们发现与人类相比，黑猩猩基因组中物种特异性L1元素的拷贝数增加，这支持了这样一种观点，即NHPs中L1迁移性的增加不仅限于培养的iPSCs，也可能发生在灵长类动物进化过程中向种系规范上游发育的种系或胚胎细胞中。我们认为，L1迁移率的差异可能对人类和NHPs的基因组产生了不同的影响，并可能具有持续的适应性意义。
Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behavior and are not amenable to genetic manipulation. We hypothesized that induced pluripotent stem cells (iPSCs) could be a unique biological resource to elucidate relevant phenotypical differences between human and NHPs and that those differences could have potential adaptation and speciation value. Here, we describe the generation and initial characterization of iPSCs from chimpanzees and bonobos as novel tools to explore factors that have contributed to great ape evolution. Comparative gene expression analysis of human and NHP iPSCs revealed differences in the regulation of Long Interspersed Nuclear Element-1 (LINE-1 or L1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution. Decreased levels of L1 restricting factors APOBEC3B (A3B) and PIWIL2 in NHP iPSCs correlated with increased L1 mobility and endogenous L1 mRNA levels. Moreover, results from manipulation of A3B and PIWIL2 levels in iPSCs supported a causal inverse relationship between levels of these proteins and L1 retrotransposition. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPSCs in culture and may have also occurred in the germline or embryonic cells developmentally upstream to germline specification during primate evolution. We propose that differences in L1 mobility may have differentially shaped the genomes of humans and NHPs and could have ongoing adaptive significance.
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DOI：
10.1146/annurev-genom-082509-141802
发表时间：
2011
影响因子：
8.7
作者：
Beck CR;Garcia-Perez JL;Badge RM;Moran JV
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影响因子：
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DOI：
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发表时间：
2003-04-29
影响因子：
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64.5
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