Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons.
Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons.
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DOI：
10.1186/s40035-018-0132-x
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发表时间：
2018
影响因子：
12.6
通讯作者：
Zheng JC
中科院分区：
文献类型：
--
作者：
Ma K;Deng X;Xia X;Fan Z;Qi X;Wang Y;Li Y;Ma Y;Chen Q;Peng H;Ding J;Li C;Huang Y;Tian C;Zheng JC
细胞替代疗法被认为是治疗神经退行性疾病的一种有前途的方法。由于胚胎干细胞来源的神经前体细胞(NPC)的伦理学问题和IPSCs的致瘤潜力，将体细胞直接重编程为多能神经前体细胞已成为细胞移植的首选方法。通过转录因子FOXG1、Sox2和Brn2的过表达，将小鼠星形胶质细胞重新编程为神经前体细胞。亚型神经元的产生受细胞类型特异性转录因子Lhx8或Foxa2/Lmx1a的力表达的影响。星形胶质细胞源性诱导的鼻咽癌与野生型鼻咽癌有很高的相似性，包括鼻咽癌特异性基因的表达、DNA甲基化模式、增殖和分化能力。AiNPs致力于前脑的识别，主要分化为谷氨酸能和GABA能神经元亚型。有趣的是，TFSLhx8和Foxa2/Lmx1a在AiNPC中的额外过表达分别促进了胆碱能和多巴胺能神经元的分化。我们的研究表明，星形胶质细胞可以转化为AiNPC，谱系承诺的AiNPC可以通过强制表达特定的TF获得其他谱系的分化潜能。了解转铁蛋白对神经元重新编程和分化的影响，将为神经退行性疾病的星形胶质细胞细胞治疗提供有价值的策略。本文的在线版本(10.1186/s400350180132-x)包含补充材料，可供授权用户使用。
Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation. Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2. The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a. Astrocyte-derived induced NPCs (AiNPCs) share high similarities, including the expression of NPC-specific genes, DNA methylation patterns, the ability to proliferate and differentiate, with the wild type NPCs. The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes. Interestingly, additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation, respectively. Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs. Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases. The online version of this article (10.1186/s40035-018-0132-x) contains supplementary material, which is available to authorized users.
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影响因子：
9.8
作者：
Heinrich C;Blum R;Gascón S;Masserdotti G;Tripathi P;Sánchez R;Tiedt S;Schroeder T;Götz M;Berninger B
通讯作者：
Berninger B
DOI：
10.1073/pnas.250471697
发表时间：
2000-12-05
影响因子：
11.1
作者：
Laywell, ED;Rakic, P;Steindler, DA
通讯作者：
Steindler, DA
DOI：
10.1073/pnas.1121003109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Lujan, Ernesto;Chanda, Soham;Wernig, Marius
通讯作者：
Wernig, Marius
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：
3.7
作者：
Addis RC;Hsu FC;Wright RL;Dichter MA;Coulter DA;Gearhart JD
通讯作者：
Gearhart JD