Induced Pluripotent Stem Cells With Six Reprogramming Factors From Prairie Vole, Which Is an Animal Model for Social Behaviors
Induced Pluripotent Stem Cells With Six Reprogramming Factors From Prairie Vole, Which Is an Animal Model for Social Behaviors
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DOI：
10.3727/096368916x690502
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Fukuda, Tomokazu
中科院分区：
文献类型：
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作者：
Katayama, Masafumi;Hirayama, Takashi;Fukuda, Tomokazu
草原田鼠表现出强烈的配对与他们的交配伙伴，他们表现出父母的行为对他们的婴儿，表明草原田鼠是一个独特的动物模型，分析的分子机制的社会行为。直到最近的一项研究，催产素的信号通路被认为是草原田鼠的社会行为的关键，但神经元特异性功能研究可能是必要的，以确定社会行为的分子机制。高质量的草原田鼠多能干细胞对于阐明社会行为的分子机制至关重要。高质量诱导多能干细胞（iPSC）的产生将有助于建立基于iPSC多能性的转基因草原田鼠，包括敲除和敲入模型。因此，我们试图在本研究中建立高质量的草原田鼠来源的iPSCs（pv-iPSCs）。我们构建了一个多顺反子重编程载体，其中包括六个重编程因子（Oct 3/4，Sox 2，Klf 4，c-myc，Lin 28和Nanog）。此外，我们评估了六种重编程因子的作用，其中包括Oct 3/4与MyoD的反式激活结构域（transactivation domain，OTT）。将pv-iPSC植入免疫缺陷小鼠中引起具有三个胚层的畸胎瘤。此外，所建立的pv-iPSCs对干细胞标志物测试呈阳性，包括碱性磷酸酶活性（ALP）、阶段特异性胚胎抗原（SSEA）-1和对白血病抑制因子（LIF）的依赖性。我们的数据表明，我们新建立的pv-iPSCs可能是社会行为遗传分析的有用工具。
Prairie voles show strong pair bonding with their mating partners, and they demonstrate parental behavior toward their infants, indicating that the prairie vole is a unique animal model for analysis of molecular mechanisms of social behavior. Until a recent study, the signaling pathway of oxytocin was thought to be critical for the social behavior of prairie voles, but neuron-specific functional research may be necessary to identify the molecular mechanisms of social behavior. Prairie vole pluripotent stem cells of high quality are essential to elucidate the molecular mechanisms of social behaviors. Generation of high-quality induced pluripotent stem cells (iPSCs) would help to establish a genetically modified prairie vole, including knockout and knock-in models, based on the pluripotency of iPSCs. Thus, we attempted to establish high-quality prairie vole-derived iPSCs (pv-iPSCs) in this study. We constructed a polycistronic reprogramming vector, which included six reprograming factors (Oct3/4, Sox2, Klf4, c-myc, Lin28, and Nanog). Furthermore, we evaluated the effect of six reprogramming factors, which included Oct3/4 with the transactivation domain (TAD) of MyoD. Implantation of the pv-iPSCs into immunodeficient mice caused a teratoma with three germ layers. Furthermore, the established pv-iPSCs tested positive for stem cell markers, including alkaline phosphatase activity (ALP), stage-specific embryonic antigen (SSEA)-1, and dependence on leukemia inhibitory factor (LIF). Our data indicate that our newly established pv-iPSCs may be a useful tool for genetic analysis of social behavior.