To induce and maintain naïve pluripotency in mouse embryonic and induced pluripotent stem cells (ESCs/iPSCs), chemically defined N2B27 medium with PD0325901, CHIR99021, and leukemia inhibitory factor (2i/LIF) is a classic and simple condition. However, this method cannot be simply extrapolated to human ESCs/iPSCs that are principally stabilized in primed pluripotency and become primitive neuroepithelium-like cells in N2B27+2i/LIF culture. Here, we assessed iPSC reprogramming of fibroblasts from chimpanzee, our closest living relative, in N2B27+2i/LIF culture. Under this condition, chimpanzee cells formed alkaline phosphatase-positive dome-shaped colonies. The colony-forming cells could be stably expanded by serial passaging without a ROCK inhibitor. However, their gene expression was distinct from iPSCs and neuroepithelium. They expressed the OCT3/4 transgene and a subset of transcripts associated with pluripotency, mesenchymal-epithelial transition, and neural crest formation. These cells exhibited a differentiation potential into the three germ layers in vivo and in vitro. The current study demonstrated that iPSC reprogramming in N2B27+2i/LIF culture converted chimpanzee fibroblasts into a multipotent cancerous state with unique gene expression, but not fully pluripotent stem cells.

为了在小鼠胚胎和诱导多能干细胞（ESCs / iPSC）中诱导和维持幼稚的多能性，化学定义的具有PD0325901，CHIR99021和白血病抑制因子（2i / LIF）的N2B27培养基是一种经典而简单的条件。然而，这种方法不能简单地外推至主要稳定在引发多能性中并在N2B27 + 2i / LIF培养中成为原始神经上皮样细胞的人ESC / iPSC。在这里，我们评估了我们最近的近亲黑猩猩在N2B27 + 2i / LIF培养中对成纤维细胞进行iPSC重编程。在这种条件下，黑猩猩细胞形成了碱性磷酸酶阳性的圆顶状菌落。不用ROCK抑制剂，可通过连续传代稳定地扩增集落形成细胞。但是，它们的基因表达不同于iPSC和神经上皮。他们表达了OCT3 / 4转基因以及与多能性，间充质-上皮转化和神经c形成相关的转录子的子集。这些细胞表现出向三个胚层的分化潜能体内和体外。当前的研究表明，在N2B27 + 2i / LIF培养物中对iPSC进行重编程可将黑猩猩成纤维细胞转变为具有独特基因表达的多能癌状态，但不能完全发挥多能干细胞的作用。