Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass.
Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass.
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DOI：
10.1016/j.stemcr.2016.02.005
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发表时间：
2016-04-12
影响因子：
5.9
通讯作者：
Nichols J
中科院分区：
文献类型：
--
作者：
Guo G;von Meyenn F;Santos F;Chen Y;Reik W;Bertone P;Smith A;Nichols J
从人胚泡常规生成干细胞产生发育晚期或致敏的多能性阶段。已经报道了在体外重置为更幼稚的表型。然而，尚未确定选择性激酶抑制的重置培养条件是否能够直接从胚胎捕获幼稚上胚层细胞。在这里，我们表明，在这些特定的条件下，单个内细胞团细胞生长成集落，然后可以在多个传代中扩增，同时保留二倍体核型和幼稚特性。这些细胞表达标志性幼稚多能性因子，并且还显示出与引发细胞不同的线粒体呼吸、全局基因表达和全基因组低甲基化的特征。它们通过引发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。与典型小鼠胚胎干细胞相似的人类胚胎干细胞则主张在哺乳动物多能性的阶段性进展中保持保守性。来源于单个人ICM细胞的核型正常的多能干细胞扩增的细胞系保留了幼稚胚胎干细胞的预期分子特征ICM来源的和体外重置幼稚人多能干细胞之间的一致性人ICM和幼稚干细胞中KLF17蛋白的存在在这篇论文中，Nichols，Smith，和同事们表明，干细胞可以通过将内细胞团解离成单细胞并在抑制进一步分化的条件下培养而从人类胚胎中获得。分子分析表明，比以前观察到的人胚胎干细胞系更幼稚的状态。
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. Karyotypically normal pluripotent stem cells derived from single human ICM cells Expanded lines retain anticipated molecular features of naive embryonic stem cells Consistency between ICM-derived and in vitro reset naive human pluripotent stem cells Presence of KLF17 protein in human ICM and naive stem cells In this paper, Nichols, Smith, and colleagues show that stem cells can be derived from human embryos by dissociation of the inner cell mass into single cells and culture in conditions that suppress further differentiation. Molecular profiling indicates a more naive status than previously observed for human embryonic stem cell lines.