Combinatorial modulation of signaling pathways reveals cell-type-specific requirements for highly efficient and synchronous iPSC reprogramming.
Combinatorial modulation of signaling pathways reveals cell-type-specific requirements for highly efficient and synchronous iPSC reprogramming.
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DOI：
10.1016/j.stemcr.2014.08.003
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发表时间：
2014-10-14
影响因子：
5.9
通讯作者：
Stadtfeld, Matthias
中科院分区：
文献类型：
--
作者：
Vidal, Simon E.;Amlani, Bhishma;Chen, Taotao;Tsirigos, Aristotelis;Stadtfeld, Matthias
体细胞的分化状态为诱导多能干细胞（iPSC）的衍生提供了障碍。为了解决为什么某些细胞类型比其他细胞更容易重编程，我们研究了细胞信号通路的联合调节的效果。令人惊讶的是，在抗坏血酸存在下抑制转化生长因子β（TGF-β）以及激活Wnt信号传导允许>80%的鼠成纤维细胞在重编程因子表达1周后获得多能性。相比之下，肝祖细胞和血祖细胞主要分别仅需要TGF-β抑制或经典Wnt激活，以接近100%的效率重编程。引人注目的是，血液祖细胞以高度同步的方式重新激活内源性多能性基因座，并且我们证明特异性染色质修饰酶的表达和TGF-β/促分裂原活化蛋白（MAP）激酶活性的降低是与这些细胞的独特重编程反应相关的内在特性。我们的观察定义了体细胞快速同步重编程的细胞类型特定要求。三种化合物混合物驱动快速有效的MEF重编程Wnt激活允许同步获得血液祖细胞中的多能性内在特性引发体细胞祖细胞转化为iPSC在这篇文章中，Stadtfeld及其同事描述了诱导体细胞多能性的细胞类型特异性障碍。作者的结果有助于解释为什么某些细胞类型特别适合iPSC重编程，并将经典Wnt信号的激活确定为高效和同步血液祖细胞重编程的主要要求。
The differentiated state of somatic cells provides barriers for the derivation of induced pluripotent stem cells (iPSCs). To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. Surprisingly, inhibition of transforming growth factor β (TGF-β) together with activation of Wnt signaling in the presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after 1 week of reprogramming factor expression. In contrast, hepatic and blood progenitors predominantly required only TGF-β inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner, and we demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF-β/mitogen-activated protein (MAP) kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Our observations define cell-type-specific requirements for the rapid and synchronous reprogramming of somatic cells. A three-compound mix drives rapid and efficient MEF reprogramming Wnt activation allows synchronous acquisition of pluripotency in blood progenitors Intrinsic properties prime somatic progenitor cells for conversion into iPSCs In this article, Stadtfeld and colleagues describe cell-type-specific barriers for the induction of pluripotency in somatic cells. The authors’ results help explain why certain cell types are particularly amenable for iPSC reprogramming and identifying activation of canonical Wnt signaling as a major requirement of highly efficient and synchronous blood progenitor cell reprogramming.
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重编程因子表达引发了广泛的靶向染色质重塑。
影响因子：
23.9
作者：
Koche RP;Smith ZD;Adli M;Gu H;Ku M;Gnirke A;Bernstein BE;Meissner A
通讯作者：
Meissner A
DOI：
10.1016/j.cub.2009.08.025
发表时间：
2009-11-03
期刊：
Current biology : CB
影响因子：
--
作者：
Maherali N;Hochedlinger K
通讯作者：
Hochedlinger K
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：
Ang YS;Tsai SY;Lee DF;Monk J;Su J;Ratnakumar K;Ding J;Ge Y;Darr H;Chang B;Wang J;Rendl M;Bernstein E;Schaniel C;Lemischka IR
通讯作者：
Lemischka IR
间充质到上皮的转变启动并且是小鼠成纤维细胞核重编程所必需的
影响因子：
23.9
作者：
Li, Ronghui;Liang, Jialiang;Pei, Duanqing
通讯作者：
Pei, Duanqing