In contrast to conventional human pluripotent stem cells (hPSCs) that are related to post-implantation embryo stages, naive hPSCs exhibit features of pre-implantation epiblast. Naive hPSCs are established by resetting conventional hPSCs, or are derived from dissociated embryo inner cell masses. Here we investigate conditions for transgene-free reprogramming of human somatic cells to naive pluripotency. We find that Wnt inhibition promotes RNA-mediated induction of naive pluripotency. We demonstrate application to independent human fibroblast cultures and endothelial progenitor cells. We show that induced naive hPSCs can be clonally expanded with a diploid karyotype and undergo somatic lineage differentiation following formative transition. Induced naive hPSC lines exhibit distinctive surface marker, transcriptome, and methylome properties of naive epiblast identity. This system for efficient, facile, and reliable induction of transgene-free naive hPSCs offers a robust platform, both for delineation of human reprogramming trajectories and for evaluating the attributes of isogenic naive versus conventional hPSCs.

与与植入后胚胎阶段相关的传统人类多能干细胞 (hPSC) 相比，初始 hPSC 表现出植入前外胚层的特征。初始 hPSC 是通过重置常规 hPSC 建立的，或者源自解离的胚胎内细胞团。在这里，我们研究将人类体细胞无转基因重编程为原始多能性的条件。我们发现 Wnt 抑制促进 RNA 介导的幼稚多能性诱导。我们展示了其在独立人成纤维细胞培养物和内皮祖细胞中的应用。我们表明，诱导的初始 hPSC 可以以二倍体核型进行克隆扩增，并在形成转变后经历体细胞谱系分化。诱导的幼稚 hPSC 系表现出幼稚外胚层特性的独特表面标记、转录组和甲基化组特性。该系统能够高效、简便、可靠地诱导无转基因的幼稚 hPSC，提供了一个强大的平台，既可用于描绘人类重编程轨迹，也可用于评估同基因幼稚 hPSC 与传统 hPSC 的属性。