Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals.

从人类胚泡中常规生成干细胞会产生发育先进的多能性阶段。据报道，体外重置为更幼稚的表型。然而，选择性激酶抑制的重置培养条件是否能够直接从胚胎中捕获幼稚外胚层细胞尚未确定。在这里，我们展示了在这些特定条件下，单个内细胞团细胞生长成菌落，然后可以在多个通道中扩增，同时保留二倍体核型和幼稚特性。这些细胞表达标志性的幼稚多能性因子，并且还显示出不同于致敏细胞的线粒体呼吸、全局基因表达和全基因组低甲基化的特征。它们通过启动的多能性转变为体细胞谱系分化。总的来说，这些属性表明分类为人类幼稚胚胎干细胞。典型小鼠胚胎干细胞的人类对应物会主张在哺乳动物多能性的分阶段进展中进行保护。