Nanog is the gateway to the pluripotent ground state.
Nanog is the gateway to the pluripotent ground state.
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DOI：
10.1016/j.cell.2009.07.039
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发表时间：
2009-08-21
期刊：
影响因子：
64.5
通讯作者：
Smith A
中科院分区：
文献类型：
--
作者：
Silva J;Nichols J;Theunissen TW;Guo G;van Oosten AL;Barrandon O;Wray J;Yamanaka S;Chambers I;Smith A
多能性是在哺乳动物发育过程中通过形成外胚层（胚胎的创始组织）而自然产生的。多能性可以通过体细胞重编程来重建。在这里，我们提出的证据表明，同源结构域蛋白Nanog介导收购胚胎和诱导多能性。通过细胞融合产生多能杂交体由Nanog促进并依赖于Nanog。在转录因子诱导的分子重编程中，Nanog最初是不稳定的，但对于去分化的中间体过渡到基态多能性变得至关重要。在胚胎中，Nanog特异性地划分新生的外胚层，与X染色体重编程的结构域一致。没有Nanog，多能性不会发展，并且内部细胞团被困在最终不能存活的多能性前的不确定状态中。这些发现表明，Nanog编排合成幼稚的上胚层基态在胚胎中，这种功能是重演体细胞重编程的高潮。
Pluripotency is generated naturally during mammalian development through formation of the epiblast, founder tissue of the embryo proper. Pluripotency can be recreated by somatic cell reprogramming. Here we present evidence that the homeodomain protein Nanog mediates acquisition of both embryonic and induced pluripotency. Production of pluripotent hybrids by cell fusion is promoted by and dependent on Nanog. In transcription factor-induced molecular reprogramming, Nanog is initially dispensable but becomes essential for dedifferentiated intermediates to transit to ground state pluripotency. In the embryo, Nanog specifically demarcates the nascent epiblast, coincident with the domain of X chromosome reprogramming. Without Nanog, pluripotency does not develop, and the inner cell mass is trapped in a pre-pluripotent, indeterminate state that is ultimately nonviable. These findings suggest that Nanog choreographs synthesis of the naive epiblast ground state in the embryo and that this function is recapitulated in the culmination of somatic cell reprogramming.
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