Nanog-independent reprogramming to iPSCs with canonical factors.
Nanog-independent reprogramming to iPSCs with canonical factors.
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DOI：
10.1016/j.stemcr.2013.12.010
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发表时间：
2014-02-11
影响因子：
5.9
通讯作者：
Eggan, Kevin
中科院分区：
文献类型：
--
作者：
Carter, Ava C.;Davis-Dusenbery, Brandi N.;Koszka, Kathryn;Ichida, Justin K.;Eggan, Kevin
已经表明，转录因子Nanog对于在胚胎干细胞和诱导多能干细胞（iPSC）的衍生期间建立多能性是必不可少的。然而，成功的重编程多能性与越来越多的不同的转录因子，在不断增加的效率，表明可能有许多不同的路线到一个pluripotent state. In这里，我们已经调查了Nanog是否是必要的重编程小鼠成纤维细胞在高效的条件下使用经典的重编程因子Oct 4，Sox 2，Klf 4，和cMyc。与先前的结果一致，Nanog−/−成纤维细胞的重编程效率显著低于对照成纤维细胞。然而，与之前的发现相反，我们能够从Nanog−/−成纤维细胞中可重复地产生iPSCs，这些成纤维细胞有效地促进了嵌合小鼠的生殖系。因此，尽管Nanog可能是重编程的重要介质，但即使在标准条件下，也不需要在小鼠中建立多能性。Nanog缺陷型iPSC有助于嵌合小鼠的生殖系。在此，Eggan等人表明，使用采用经典KSOM因子的高效重编程条件能够从Nanog缺陷型MEF衍生嵌合体和生殖系感受态iPSC。这反驳了先前的观点，即Nanog是多能状态的重要守门人，并强调了多能性有多种途径。
It has been suggested that the transcription factor Nanog is essential for the establishment of pluripotency during the derivation of embryonic stem cells and induced pluripotent stem cells (iPSCs). However, successful reprogramming to pluripotency with a growing list of divergent transcription factors, at ever-increasing efficiencies, suggests that there may be many distinct routes to a pluripotent state. Here, we have investigated whether Nanog is necessary for reprogramming murine fibroblasts under highly efficient conditions using the canonical-reprogramming factors Oct4, Sox2, Klf4, and cMyc. In agreement with prior results, the efficiency of reprogramming Nanog−/− fibroblasts was significantly lower than that of control fibroblasts. However, in contrast to previous findings, we were able to reproducibly generate iPSCs from Nanog−/− fibroblasts that effectively contributed to the germline of chimeric mice. Thus, whereas Nanog may be an important mediator of reprogramming, it is not required for establishing pluripotency in the mouse, even under standard conditions. Nanog is not required for canonical reprogramming of murine fibroblasts to iPSCs Nanog-deficient iPSCs contribute to the germline of chimeric mice Here, Eggan et al. show that using highly efficient reprogramming conditions employing canonical KSOM factors enables derivation of chimera- and germline-competent iPSCs from Nanog-deficient MEFs. This counters the previous notion that Nanog is an essential gatekeeper to the pluripotent state and highlights that there are multiple routes to pluripotency.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
9.8
作者：
Silva, Jose;Barrandon, Ornella;Nichols, Jennifer;Kawaguchi, Jitsutaro;Theunissen, Thorold W.;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
23.9
作者：
Ichida JK;Blanchard J;Lam K;Son EY;Chung JE;Egli D;Loh KM;Carter AC;Di Giorgio FP;Koszka K;Huangfu D;Akutsu H;Liu DR;Rubin LL;Eggan K
通讯作者：
Eggan K
影响因子：
64.5
作者：
Silva J;Nichols J;Theunissen TW;Guo G;van Oosten AL;Barrandon O;Wray J;Yamanaka S;Chambers I;Smith A
通讯作者：
Smith A