The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes.
The let-7/LIN-41 pathway regulates reprogramming to human induced pluripotent stem cells by controlling expression of prodifferentiation genes.
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DOI：
10.1016/j.stem.2013.11.001
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发表时间：
2014-01-02
期刊：
影响因子：
23.9
通讯作者：
Yamanaka, Shinya
中科院分区：
文献类型：
--
作者：
Worringer, Kathleen A.;Rand, Tim A.;Hayashi, Yohei;Sami, Salma;Takahashi, Kazutoshi;Tanabe, Koji;Narita, Megumi;Srivastava, Deepak;Yamanaka, Shinya
将分化细胞重编程为诱导多能干细胞 (iPSC) 可促进广泛的细胞变化。在这里，我们展示了 microRNA 的 let-7 家族通过涉及促分化因子（包括 EGR1）的调节途径对重编程过程发挥抑制作用。当与 OCT4、SOX2 和 KLF4 结合时，抑制人类细胞中的 let-7 可促进重编程，其程度与 c-MYC 相当，并且 let-7 的持续存在会抑制重编程。在重编程过程中抑制let-7会导致let-7靶标LIN-41/TRIM71水平增加，这反过来又促进重编程，对于克服let-7重编程障碍非常重要。机制研究表明，LIN-41 调节多种分化基因，更具体地说，通过结合其同源 mRNA 来抑制 EGR1 的翻译。我们的研究结果共同概述了一条基于let-7的途径，该途径通过促进促分化基因的表达来抵消重编程因子的活性。
Reprogramming differentiated cells into induced pluripotent stem cells (iPSCs) promotes a broad array of cellular changes. Here we show that the let-7 family of microRNAs acts as an inhibitory influence on the reprogramming process through a regulatory pathway involving pro-differentiation factors, including EGR1. Inhibiting let-7 in human cells promotes reprogramming to a comparable extent to c-MYC when combined with OCT4, SOX2, and KLF4, and persistence of let-7 inhibits reprogramming. Inhibiting let-7 during reprogramming leads to an increase in the level of the let-7 target LIN-41/TRIM71, which in turn promotes reprogramming and is important for overcoming the let-7 barrier to reprogramming. Mechanistic studies revealed that LIN-41 regulates a broad array of differentiation genes, and more specifically, inhibits translation of EGR1 through binding its cognate mRNA. Together our findings outline a let-7 based pathway that counteracts the activity of reprogramming factors through promoting the expression of pro-differentiation genes.
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转录因子早期生长响应1（EGR-1）的进步pre-B和未成熟B细胞的分化。
DOI：
10.1084/jem.188.12.2215
发表时间：
1998-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dinkel A;Warnatz K;Ledermann B;Rolink A;Zipfel PF;Bürki K;Eibel H
通讯作者：
Eibel H
影响因子：
64.5
作者：
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通讯作者：
Singh, Harinder
影响因子：
4
作者：
Kumbrink, Joerg;Kirsch, Kathrin H.;Johnson, Judith P.
通讯作者：
Johnson, Judith P.
影响因子：
5.3
作者：
CAO, XM;KOSKI, RA;SUKHATME, VP
通讯作者：
SUKHATME, VP
影响因子：
11.2
作者：
Johnson, Charles D.;Esquela-Kerscher, Aurora;Slack, Frank J.
通讯作者：
Slack, Frank J.