The iNs and Outs of Direct Reprogramming to Induced Neurons.
The iNs and Outs of Direct Reprogramming to Induced Neurons.
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DOI：
10.3389/fgeed.2020.00007
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发表时间：
2020
影响因子：
--
通讯作者：
Fink KD
中科院分区：
文献类型：
--
作者：
Carter JL;Halmai JANM;Fink KD
对细胞类型特异性转录因子的了解促进了细胞重编程方法的进展，例如直接重编程体细胞以诱导神经元（in）。直接重编程的方法需要通过神经元特异性microrna、关键神经元信号通路的化学调节或通过病毒载体的过表达来决定神经元命运，而一些重编程策略需要结合这些方法来诱导神经元细胞命运。这些方法已应用于多种细胞类型，包括成纤维细胞、肝细胞、外周血单核细胞和T细胞。从皮肤活检和血液样本中产生iN的能力，加上人工诱导年龄和疾病相关表型的最新进展，正在加速迟发性神经退行性疾病疾病模型的发展。在这里，我们回顾了神经元转录组的激活如何改变供体细胞的表观遗传景观，以促进神经元的重编程。我们还讨论了利用DNA结合域（如CRISPR/dCas9）克服表观遗传障碍，通过激活内源性神经元细胞命运决定基因来诱导神经元细胞命运的优势。
Understanding of cell-type specific transcription factors has promoted progress in methods for cellular reprogramming, such as directly reprogramming somatic cells to induced neurons (iN). Methods for direct reprogramming require neuronal-fate determining gene activation via neuron-specific microRNAs, chemical modulation of key neuronal signaling pathways or overexpression via viral vectors, with some reprogramming strategies requiring a combination of these methods to induce the neuronal-cell fate. These methods have been employed in a multitude of cell types, including fibroblasts, hepatocytes, peripheral blood mononuclear, and T cells. The ability to create iN from skin biopsies and blood samples coupled with recent advancements in artificially inducing age- and disease-associated phenotypes are accelerating the development of disease models for late-onset neurodegenerative disorders. Here, we review how activation of the neuronal transcriptome alters the epigenetic landscape of the donor cell to facilitate reprogramming to neurons. We also discuss the advantages of using DNA binding domains such as CRISPR/dCas9 to overcome epigenetic barriers to induce neuronal-cell fate by activating endogenous neuronal cell-fate determining genes.
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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
影响因子：
25
作者：
Guo, Junjie U.;Su, Yijing;Shin, Joo Heon;Shin, Jaehoon;Li, Hongda;Xie, Bin;Zhong, Chun;Hu, Shaohui;Le, Thuc;Fan, Guoping;Zhu, Heng;Chang, Qiang;Gao, Yuan;Ming, Guo-li;Song, Hongjun
通讯作者：
Song, Hongjun
影响因子：
11
作者：
Bardy, C.;van den Hurk, M.;Kakaradov, B.;Erwin, J. A.;Jaeger, B. N.;Hernandez, R. V.;Eames, T.;Paucar, A. A.;Gorris, M.;Marchand, C.;Jappelli, R.;Barron, J.;Bryant, A. K.;Kellogg, M.;Lasken, R. S.;Rutten, B. P. F.;Steinbusch, H. W. M.;Yeo, G. W.;Gage, F. H.
通讯作者：
Gage, F. H.
影响因子：
23.9
作者：
Han, Dong Wook;Tapia, Natalia;Schoeler, Hans R.
通讯作者：
Schoeler, Hans R.
影响因子：
5.9
作者：
Chanda, Soham;Ang, Cheen Euong;Davila, Jonathan;Pak, ChangHui;Mall, Moritz;Lee, Qian Yi;Ahlenius, Henrik;Jung, Seung Woo;Suedhof, Thomas C.;Wernig, Marius
通讯作者：
Wernig, Marius