Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons

作     者：Kangmu Ma Xiaobei Deng Xiaohuan Xia Zhaohuan Fan Xinrui Qi Yongxiang Wang Yuju Li Yizhao Ma Qiang Chen Hui Peng Jianqing Ding Chunhong Li Yunlong Huang Changhai Tian Jialin C.Zheng 

作者机构：Center for Translational Neurodegeneration and Regenerative TherapyShanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineShanghai 200072China Collaborative Innovation Center for Brain ScienceTongji UniversityShanghai 200092China Departments of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaNE 68198-5930USA Department of Neurology&Institute of NeurologyRuijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaNE 68198-5930USA 

出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)

年 卷 期：2018年第7卷第1期

页      面：307-321页

核心收录：

学科分类：0710[理学-生物学] 0402[教育学-心理学(可授教育学、理学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 1010[医学-医学技术（可授医学、理学学位）] 100101[医学-人体解剖与组织胚胎学] 1009[医学-特种医学] 10[医学] 

基　　金：This work was supported in part by research grants from the National Basic Research Program of China(973 ProgramGrant No.2014CB965001 to JZ) Innovative Research Groups of the National Natural Science Foundation of China(#81221001 to JZ) Joint Research Fund for Overseas Chinese,Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China(#81329002 to JZ) the National Institutes of Health:2R56NS041858-15A1(JZ),1R01NS097195-01(JZ),and R03 NS094071-01(YH) the State of Nebraska,DHHS-LB606 Stem Cell 2009-10 to JZ 

主　　题：Astrocytes iNPCs Reprogramming Transcription factor Neuronal lineage Cholinergic neurons Dopaminergic neurons Lhx8 Foxa2 Lmx1a 

摘      要：Background:Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative *** 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 ***:Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors(TFs)Foxg1,Sox2,and *** generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/***: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 *** AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal ***,additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation,***: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 *** 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.