首页> 中文期刊> 《转化神经变性病(英文)》 >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

         

摘要

Background: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.Methods: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.Results: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.Conclusions: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.

著录项

  • 来源
    《转化神经变性病(英文)》 |2018年第1期|P.307-321|共15页
  • 作者单位

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 ChinaDepartments of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha NE 68198-5930 USA;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 China;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 China;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 China;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 China;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 ChinaDepartments of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha NE 68198-5930 USA;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 ChinaDepartments of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha NE 68198-5930 USA;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 China;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 ChinaDepartments of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha NE 68198-5930 USA;

    Departments of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha NE 68198-5930 USA;

    Department of Neurology&Institute of Neurology Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200025 China;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 China;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 ChinaDepartments of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha NE 68198-5930 USA;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 ChinaDepartments of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha NE 68198-5930 USA;

    Center for Translational Neurodegeneration and Regenerative Therapy Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine Shanghai 200072 ChinaCollaborative Innovation Center for Brain Science Tongji University Shanghai 200092 ChinaDepartments of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha NE 68198-5930 USADepartment of Pathology and Microbiology University of Nebraska Medical Center Omaha NE 68198-5930 USA;

  • 原文格式 PDF
  • 正文语种 chi
  • 中图分类 人体形态学;
  • 关键词

    Astrocytes; iNPCs; Reprogramming; Transcription factor; Neuronal lineage; Cholinergic neurons; Dopaminergic neurons; Lhx8; Foxa2; Lmx1a;

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