Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Discovery Research Laboratories I, Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.
Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Stem Cell Reports. 2017 Dec 12;9(6):1825-1838. doi: 10.1016/j.stemcr.2017.10.008. Epub 2017 Nov 9.
Several groups have reported the existence of a form of pluripotency that resembles that of mouse embryonic stem cells (mESCs), i.e., a naive state, in human pluripotent stem cells; however, the characteristics vary between reports. The nuclear receptor ESRRB is expressed in mESCs and plays a significant role in their self-renewal, but its expression has not been observed in most naive-like human induced pluripotent stem cells (hiPSCs). In this study, we modified several methods for converting hiPSCs into a naive state through the transgenic expression of several reprogramming factors. The resulting cells express the components of the core transcriptional network of mESCs, including ESRRB, at high levels, which suggests the existence of naive-state hiPSCs that are similar to mESCs. We also demonstrate that these cells differentiate more readily into neural cells than do conventional hiPSCs. These features may be beneficial for their use in disease modeling and regenerative medicine.
几个研究小组已经报道了在人类多能干细胞中存在类似于小鼠胚胎干细胞(mESCs)的多能性形式,即原始状态;然而,这些报告之间存在差异。核受体 ESRRB 在 mESCs 中表达,并在其自我更新中发挥重要作用,但在大多数类似原始的人类诱导多能干细胞(hiPSCs)中并未观察到其表达。在这项研究中,我们通过转基因表达几种重编程因子来修改几种将 hiPSCs 转化为原始状态的方法。得到的细胞高表达 mESCs 核心转录网络的组成部分,包括 ESRRB,这表明存在类似于 mESCs 的原始状态 hiPSCs。我们还证明这些细胞比传统的 hiPSCs 更容易分化为神经细胞。这些特征可能有益于它们在疾病建模和再生医学中的应用。