Mechanistic Insights Into MicroRNA-Induced Neuronal Reprogramming of Human Adult Fibroblasts.
Mechanistic Insights Into MicroRNA-Induced Neuronal Reprogramming of Human Adult Fibroblasts.
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DOI：
10.3389/fnins.2018.00522
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发表时间：
2018
影响因子：
4.3
通讯作者：
Yoo AS
中科院分区：
文献类型：
--
作者：
Lu YL;Yoo AS
使用转录因子作为细胞命运调节器通常是体细胞直接重编程为神经元的主要关注点。然而，在人类成年成纤维细胞中，高效地获得功能成熟的神经元需要额外的神经生成因子，如microRNAs(MiRNAs)，以唤起转录因子允许的神经元状态，以发挥其重编程活性。因此，越来越多的证据表明，大脑丰富的miRNA，miR-9/9∗和miR-124，通过同时靶向抗神经源性效应器，同时允许额外的转录因子产生特定亚型的人类神经元，是强大的神经源性分子。在这篇综述中，我们将重点介绍利用神经元miRNAs的方法，并提供机制方面的见解，通过神经元miRNAs与脑区特异性转录因子的协同作用，推动人成纤维细胞转化为临床相关的神经元亚型。此外，我们将深入了解直接转化的神经元的年龄特征，以及如何利用转化的人类神经元来模拟迟发性神经退行性疾病。
The use of transcriptional factors as cell fate regulators are often the primary focus in the direct reprogramming of somatic cells into neurons. However, in human adult fibroblasts, deriving functionally mature neurons with high efficiency requires additional neurogenic factors such as microRNAs (miRNAs) to evoke a neuronal state permissive to transcription factors to exert their reprogramming activities. As such, increasing evidence suggests brain-enriched miRNAs, miR-9/9∗ and miR-124, as potent neurogenic molecules through simultaneously targeting of anti-neurogenic effectors while allowing additional transcription factors to generate specific subtypes of human neurons. In this review, we will focus on methods that utilize neuronal miRNAs and provide mechanistic insights by which neuronal miRNAs, in synergism with brain-region specific transcription factors, drive the conversion of human fibroblasts into clinically relevant subtypes of neurons. Furthermore, we will provide insights into the age signature of directly converted neurons and how the converted human neurons can be utilized to model late-onset neurodegenerative disorders.
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影响因子：
25
作者：
Blanchard, Joel W.;Eade, Kevin T.;Szucs, Attila;Lo Sardo, Valentina;Tsunemoto, Rachel K.;Williams, Daniel;Sanna, Pietro Paolo;Baldwin, Kristin K.
通讯作者：
Baldwin, Kristin K.
DOI：
10.1523/jneurosci.0558-12.2012
发表时间：
2012-06-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Åkerblom M;Sachdeva R;Barde I;Verp S;Gentner B;Trono D;Jakobsson J
通讯作者：
Jakobsson J
影响因子：
25
作者：
Chesi, Alessandra;Staahl, Brett T.;Jovicic, Ana;Couthouis, Julien;Fasolino, Maria;Raphael, Alya R.;Yamazaki, Tomohiro;Elias, Laura;Polak, Meraida;Kelly, Crystal;Williams, Kelly L.;Fifita, Jennifer A.;Maragakis, Nicholas J.;Nicholson, Garth A.;King, Oliver D.;Reed, Robin;Crabtree, Gerald R.;Blair, Ian P.;Glass, Jonathan D.;Gitler, Aaron D.
通讯作者：
Gitler, Aaron D.
影响因子：
23.9
作者：
Abernathy DG;Kim WK;McCoy MJ;Lake AM;Ouwenga R;Lee SW;Xing X;Li D;Lee HJ;Heuckeroth RO;Dougherty JD;Wang T;Yoo AS
通讯作者：
Yoo AS
Dnmt1 和 Dnmt3a 维持 DNA 甲基化并调节成人前脑神经元的突触功能
影响因子：
25
作者：
Feng, Jian;Zhou, Yu;Campbell, Susan L.;Le, Thuc;Li, En;Sweatt, J. David;Silva, Alcino J.;Fan, Guoping
通讯作者：
Fan, Guoping