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Tox4 modulates cell fate reprogramming.
Journal of Cell Science ( IF 4 ) Pub Date : 2019-10-22 , DOI: 10.1242/jcs.232223
Lotte Vanheer 1 , Juan Song 1 , Natalie De Geest 1 , Adrian Janiszewski 1 , Irene Talon 1 , Caterina Provenzano 1 , Taeho Oh 1 , Joel Chappell 1 , Vincent Pasque 2
Affiliation  

Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA-mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified Tox4 as a novel factor that modulates cell fate through an assay that determined the efficiency of iPSC reprogramming. We found that Tox4 is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of the reprogramming conditions used. Tox4 enables proper exogenous reprogramming factor expression, and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that the TOX4 protein assembles into a high molecular form. Moreover, Tox4 is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of Tox4 in modulating cell fate. Our study reveals Tox4 as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.This article has an associated First Person interview with the first author of the paper.

中文翻译:

Tox4调节细胞命运的重编程。

重新编程为诱导多能性可诱导体细胞身份向诱导多能干细胞(iPSC)的转换。但是,调解人和重编程机制在很大程度上仍不清楚。为了阐明介体和重编程机制,我们在体细胞转化为iPSC的过程中使用了siRNA介导的敲除方法来选择候选基因。我们通过确定iPSC重编程效率的测定法将Tox4鉴定为一种可调节细胞命运的新型因子。我们发现,无论使用何种重编程条件,Tox4都需要在重编程的早期阶段有效地生成早期的重编程中间产物。Tox4支持正确的外源重编程因子表达,并在重编程过程中尽早关闭和打开假定的体细胞和多能性增强剂,分别。我们表明,TOX4蛋白组装成高分子形式。此外,Tox4对于成纤维细胞向神经元命运的有效转化也是必需的,这表明Tox4在调节细胞命运方面具有更广泛的作用。我们的研究揭示了Tox4是一种细胞命运的新型转录调节因子,它介导了从体细胞状态到多能性和神经元命运的重编程。
更新日期:2019-11-01
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