Division of Animal Sciences, University of Missouri, Columbia, Missouri 65211-7310.
Division of Animal Sciences, University of Missouri, Columbia, Missouri 65211-7310.
J Biol Chem. 2011 Aug 19;286(33):28948-28953. doi: 10.1074/jbc.M111.229468. Epub 2011 Jun 24.
The pig is important for agriculture and as an animal model in human and veterinary medicine, yet despite over 20 years of effort, there has been a failure to generate pluripotent stem cells analogous to those derived from mouse embryos. Here we report the production of leukemia inhibitory factor-dependent, so-called naive type, pluripotent stem cells from the inner cell mass of porcine blastocysts by up-regulating expression of KLF4 and POU5F1. The alkaline phosphatase-positive colonies resulting from reprogramming resemble mouse embryonic stem cells in colony morphology, cell cycle interval, transcriptome profile, and expression of pluripotent markers, such as POU5F1, SOX2, and surface marker SSEA1. They are dependent on leukemia inhibitory factor signaling for maintenance of pluripotency, can be cultured over extended passage, and have the ability to form teratomas. These cells derived from the inner cell mass of pig blastocysts are clearly distinct from the FGF2-dependent "primed" induced pluripotent stem cells described recently from porcine mesenchymal cells. The data are consistent with the hypothesis that the up-regulation of KLF4, as well as POU5F1, is required to create and stabilize the naive pluripotent state and may explain why the derivation of embryonic stem cells from pigs and other ungulates has proved so difficult.
猪在农业和人类及兽医医学动物模型中具有重要作用，但尽管经过 20 多年的努力，仍然未能生成类似于从小鼠胚胎中获得的多能干细胞。在这里，我们报告了通过上调 KLF4 和 POUSF1 的表达，从猪囊胚的内细胞团中产生白血病抑制因子依赖性的所谓原始型多能干细胞。这种重编程产生的碱性磷酸酶阳性集落在集落形态、细胞周期间隔、转录组谱和多能标志物（如 POUSF1、SOX2 和表面标志物 SSEA1）的表达上类似于小鼠胚胎干细胞。它们依赖于白血病抑制因子信号来维持多能性，可以进行长时间培养，并具有形成畸胎瘤的能力。这些来自猪囊胚内细胞团的细胞与最近从猪间充质细胞中描述的 FGF2 依赖性“初始”诱导多能干细胞明显不同。这些数据与以下假设一致，即上调 KLF4 以及 POUSF1 是创建和稳定原始多能状态所必需的，这可能解释了为什么从猪和其他有蹄类动物中获得胚胎干细胞如此困难。
