Department of Physiology, School of Medicine, Keio University, Tokyo, Japan.
Laboratory for Marmoset Neural Architecture, RIKEN Center for Brain Science, Wako, Japan.
Stem Cells Dev. 2020 Jun 15;29(12):761-773. doi: 10.1089/scd.2019.0259. Epub 2020 Apr 27.
Mammalian pluripotent stem cells are thought to exist in two states: naive and primed. Generally, unlike those in rodents, pluripotent stem cells in primates, including humans, are regarded as being in the primed pluripotent state. Recently, several groups reported the existence of naive pluripotent stem cells in humans. In this study, we report the conversion of primed state embryonic stem cells from common marmoset, a New World monkey, to the naive state using transgenes. The cells showed typical naive state features, including dome-like colony morphology, growth factor requirement, gene expression profile, X chromosome activation state, and energy metabolic status. Moreover, interspecies chimeric embryo formation ability with mouse embryos was increased in the naive state. This technique can be applied in basic medical research using nonhuman primates, such as preclinical use of naive pluripotent stem cells and generating genetically modified primates.
原始态和起始态。通常情况下,与啮齿动物不同,包括人类在内的灵长类动物的多能干细胞被认为处于起始态多能状态。最近,有几个研究小组报道了在人类中存在原始态多能干细胞。在这项研究中,我们报告了使用转基因将来自新世界猴——普通狨猴的起始态胚胎干细胞转化为原始态的过程。这些细胞表现出典型的原始态特征,包括穹顶状集落形态、生长因子需求、基因表达谱、X 染色体激活状态和能量代谢状态。此外,在原始态下,与小鼠胚胎形成种间嵌合体胚胎的能力也得到了提高。这项技术可应用于使用非人类灵长类动物的基础医学研究,例如原始态多能干细胞的临床前应用和基因修饰灵长类动物的产生。