Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons
Abstract 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 e...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40035-018-0132-x |
| _version_ | 1819151853901840384 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kangmu Ma |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-22T14:40:00Z |
| format | Article |
| id | doaj.art-ca88b3fbd53e4b93a751908f56a48e80 |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-12-22T14:40:00Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-ca88b3fbd53e4b93a751908f56a48e802022-12-21T18:22:34ZengBMCTranslational Neurodegeneration2047-91582018-11-017111510.1186/s40035-018-0132-xDirect conversion of mouse astrocytes into neural progenitor cells and specific lineages of neuronsKangmu Ma0Xiaobei Deng1Xiaohuan Xia2Zhaohuan Fan3Xinrui Qi4Yongxiang Wang5Yuju Li6Yizhao Ma7Qiang Chen8Hui Peng9Jianqing Ding10Chunhong Li11Yunlong Huang12Changhai Tian13Jialin C. Zheng14Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineDepartments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical CenterDepartment of Neurology & Institute of Neurology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineCenter for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital affiliated to Tongji University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s40035-018-0132-xAstrocytesiNPCsReprogrammingTranscription factorNeuronal lineageCholinergic neurons |
| spellingShingle | 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 Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons Translational Neurodegeneration Astrocytes iNPCs Reprogramming Transcription factor Neuronal lineage Cholinergic neurons |
| title | Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons |
| title_full | Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons |
| title_fullStr | Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons |
| title_full_unstemmed | Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons |
| title_short | Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons |
| title_sort | direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons |
| topic | Astrocytes iNPCs Reprogramming Transcription factor Neuronal lineage Cholinergic neurons |
| url | http://link.springer.com/article/10.1186/s40035-018-0132-x |
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