Notch inhibition allows oncogene-independent generation of iPS cells.
Notch inhibition allows oncogene-independent generation of iPS cells.
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Notch抑制允许与癌基因无关的IPS细胞产生。
DOI：
10.1038/nchembio.1552
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发表时间：
2014-08
影响因子：
14.8
通讯作者：
Eggan, Kevin
中科院分区：
文献类型：
--
作者：
Ichida, Justin K.;Julia, T. C. W.;Williams, Luis A.;Carter, Ava C.;Shi, Yingxiao;Moura, Marcelo T.;Ziller, Michael;Singh, Sean;Amabile, Giovanni;Bock, Christoph;Umezawa, Akihiro;Rubin, Lee L.;Bradner, James E.;Akutsu, Hidenori;Meissner, Alexander;Eggan, Kevin
利用已定义的转录因子对体细胞进行重编程，使其具有多能性，这在生物医学领域具有很大的前景。然而，人类重编程仍然是低效的，依赖于潜在危险的致癌基因KLF4和CMYC的使用或肿瘤抑制基因p53的遗传抑制。我们假设在发育过程中抑制促进目标体细胞分化的信号转导通路可能会减轻iPSC重编程过程中对非核心多能性因子的需求。在这里，我们发现Notch的抑制显著提高了小鼠和人角质形成细胞iPSC生成的效率，通过以p53独立的方式抑制p21，从而富集能够长期自我更新的未分化细胞。Notch的药理抑制使不含KLF4和CMYC的人多能干细胞的常规生产成为可能，同时保持p53活性不变。因此，通过改变细胞间通讯来限制体细胞的发育，可以产生更安全的人类多能干细胞。
The reprogramming of somatic cells to pluripotency using defined transcription factors holds great promise for biomedicine. However, human reprogramming remains inefficient and relies either on the use of the potentially dangerous oncogenes KLF4 and CMYC or the genetic inhibition of the tumor suppressor gene p53. We hypothesized that inhibition of signal transduction pathways that promote differentiation of the target somatic cells during development might relieve the requirement for non-core pluripotency factors during iPSC reprogramming. Here, we show that inhibition of Notch significantly improves the efficiency of iPSC generation from mouse and human keratinocytes by suppressing p21 in a p53-independent manner and thereby enriching for undifferentiated cells capable of long-term self-renewal. Pharmacological inhibition of Notch enabled routine production of human iPSCs without KLF4 and CMYC while leaving p53 activity intact. Thus, restricting the development of somatic cells by altering intercellular communication enables the production of safer human iPSCs.
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影响因子：
14.8
作者：
Aasen, Trond;Izpisua Belmonte, Juan Carlos
通讯作者：
Izpisua Belmonte, Juan Carlos
影响因子：
3.7
作者：
Lee YL;Peng Q;Fong SW;Chen AC;Lee KF;Ng EH;Nagy A;Yeung WS
通讯作者：
Yeung WS
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：
19
作者：
Federation, Alexander J.;Bradner, James E.;Meissner, Alexander
通讯作者：
Meissner, Alexander
影响因子：
46.9
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
通讯作者：
Melton, Douglas A.