Direct reprogramming of Huntington's disease patient fibroblasts into neuron-like cells leads to abnormal neurite outgrowth, increased cell death, and aggregate formation.
Direct reprogramming of Huntington's disease patient fibroblasts into neuron-like cells leads to abnormal neurite outgrowth, increased cell death, and aggregate formation.
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DOI：
10.1371/journal.pone.0109621
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Liu Y;Xue Y;Ridley S;Zhang D;Rezvani K;Fu XD;Wang H
最近在一种类型的细胞向另一种类型的细胞的反式分化方面的进展使得通过细胞系特异的转录因子或RNA处理来直接将亨廷顿病(HD)患者的成纤维细胞转化为神经元成为可能。然而，这种可能性尚未得到检验。在这里，我们证明了HD患者来源的成纤维细胞可以通过敲除编码多嘧啶结合蛋白的单个基因的表达而直接反式分化为神经元样细胞。直接转化的HD神经元样细胞表达Tuj1、NeuN、DARPP-32和γ-氨基丁酸，表现为神经元破裂、神经分支异常、细胞死亡增加和突变型亨廷顿蛋白聚集。这些观察表明，HD患者成纤维细胞直接转化的神经元样细胞概括了HD神经病理特征的主要方面，从而为理解HD的紊乱和治疗药物的有效性提供了另一种模型。
Recent advances in trans-differentiation of one type cell to another have made it possible to directly convert Huntington’s disease (HD) patient fibroblasts into neurons by modulation of cell-lineage-specific transcription factors or RNA processing. However, this possibility has not been examined. Here, we demonstrate that HD patient-derived fibroblasts can be directly trans-differentiated into neuron-like cells by knockdown of the expression of a single gene encoding the polypyrimidine-tract-binding protein. The directly converted HD neuron-like cells were positive in expression of Tuj1, NeuN, DARPP-32, and γ-aminobutyric acid and exhibited neuritic breakdown, abnormal neuritic branching, increased cell death, and aggregation of mutant huntingtin. These observations indicate that the neuron-like cells directly converted from HD patient fibroblasts recapitulate the major aspects of neuropathological characteristics of HD and thus provide an additional model for understanding the disorder and validation of therapeutic reagents.
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影响因子：
64.5
作者：
Park IH;Arora N;Huo H;Maherali N;Ahfeldt T;Shimamura A;Lensch MW;Cowan C;Hochedlinger K;Daley GQ
通讯作者：
Daley GQ
通过确定的因素将成纤维细胞直接转化为功能性神经元。
影响因子：
64.8
作者：
Vierbuchen, Thomas;Ostermeier, Austin;Pang, Zhiping P.;Kokubu, Yuko;Suedhof, Thomas C.;Wernig, Marius
通讯作者：
Wernig, Marius
DOI：
10.1083/jcb.200306038
发表时间：
2003-10-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Zhou H;Cao F;Wang Z;Yu ZX;Nguyen HP;Evans J;Li SH;Li XJ
通讯作者：
Li XJ
影响因子：
4.8
作者：
Dong, Gaofeng;Callegari, Eduardo A.;Wang, Hongmin
通讯作者：
Wang, Hongmin
影响因子：
5.3
作者：
Rong, Juan;McGuire, John R.;Li, Xiao-Jiang
通讯作者：
Li, Xiao-Jiang