Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors
Summary: Oligodendrocyte spheroids (OL-spheroids) containing oligodendrocytes and neurons provide an accessible system to dissect demyelinating diseases and test therapeutic treatment. However, generation of human OL-spheroids is still technically challenging and time-consuming until now. Here, we p...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222014444 |
| _version_ | 1797996551043284992 |
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| author | Ling Ma Yuting Mei Peibo Xu Yan Cheng Zhiwen You Xiaoli Ji Deyi Zhuang Wenhao Zhou Yuejun Chen Man Xiong |
| author_facet | Ling Ma Yuting Mei Peibo Xu Yan Cheng Zhiwen You Xiaoli Ji Deyi Zhuang Wenhao Zhou Yuejun Chen Man Xiong |
| author_sort | Ling Ma |
| collection | DOAJ |
| description | Summary: Oligodendrocyte spheroids (OL-spheroids) containing oligodendrocytes and neurons provide an accessible system to dissect demyelinating diseases and test therapeutic treatment. However, generation of human OL-spheroids is still technically challenging and time-consuming until now. Here, we presented evidence that overexpression of SOX10 and OLIG2 (SO) in human embryonic stem cells (hESCs)-derived ventral forebrain neural progenitors is sufficient to produce forebrain pre-oligodendrocytes (pre-OLs) and mature oligodendrocytes (OLs) within 20–40 days. More importantly, optimizing this procedure by overexpression of SO in ventral forebrain spheroids, we successfully generated OL-spheroids with pre-OLs, mature OLs, and neurons 40 days after OL-induction. We further demonstrated oligodendrocyte-neuron interactions and obvious axon myelination in OL-spheroids. Finally, over 30% cells developed into mature oligodendrocytes with forebrain identity and myelinate axons in mouse brain 3 months after transplantation. This study provides a strategy to generate forebrain OL-spheroids rapidly and efficiently which would facilitate development of new therapeutics for demyelinating disorders. |
| first_indexed | 2024-04-11T10:19:08Z |
| format | Article |
| id | doaj.art-1654d360ceb942679d5f93300a354733 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T10:19:08Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-1654d360ceb942679d5f93300a3547332022-12-22T04:29:49ZengElsevieriScience2589-00422022-10-012510105172Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factorsLing Ma0Yuting Mei1Peibo Xu2Yan Cheng3Zhiwen You4Xiaoli Ji5Deyi Zhuang6Wenhao Zhou7Yuejun Chen8Man Xiong9Stem Cell Center of Children’s Hospital, Fudan University, Shanghai 201102, ChinaStem Cell Center of Children’s Hospital, Fudan University, Shanghai 201102, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, ChinaStem Cell Center of Children’s Hospital, Fudan University, Shanghai 201102, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, ChinaFujian Key Laboratory of Neonatal Diseases, Xiamen Key Laboratory of Neonatal Diseases, Xiamen Children’s Hospital, Xiamen 361006, ChinaCenter for Molecular Medicine, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, ChinaInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, ChinaState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China; Corresponding authorSummary: Oligodendrocyte spheroids (OL-spheroids) containing oligodendrocytes and neurons provide an accessible system to dissect demyelinating diseases and test therapeutic treatment. However, generation of human OL-spheroids is still technically challenging and time-consuming until now. Here, we presented evidence that overexpression of SOX10 and OLIG2 (SO) in human embryonic stem cells (hESCs)-derived ventral forebrain neural progenitors is sufficient to produce forebrain pre-oligodendrocytes (pre-OLs) and mature oligodendrocytes (OLs) within 20–40 days. More importantly, optimizing this procedure by overexpression of SO in ventral forebrain spheroids, we successfully generated OL-spheroids with pre-OLs, mature OLs, and neurons 40 days after OL-induction. We further demonstrated oligodendrocyte-neuron interactions and obvious axon myelination in OL-spheroids. Finally, over 30% cells developed into mature oligodendrocytes with forebrain identity and myelinate axons in mouse brain 3 months after transplantation. This study provides a strategy to generate forebrain OL-spheroids rapidly and efficiently which would facilitate development of new therapeutics for demyelinating disorders.http://www.sciencedirect.com/science/article/pii/S2589004222014444Biological sciencesCellular neuroscienceBiotechnologyStem cells researchCell biology |
| spellingShingle | Ling Ma Yuting Mei Peibo Xu Yan Cheng Zhiwen You Xiaoli Ji Deyi Zhuang Wenhao Zhou Yuejun Chen Man Xiong Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors iScience Biological sciences Cellular neuroscience Biotechnology Stem cells research Cell biology |
| title | Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors |
| title_full | Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors |
| title_fullStr | Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors |
| title_full_unstemmed | Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors |
| title_short | Fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors |
| title_sort | fast generation of forebrain oligodendrocyte spheroids from human embryonic stem cells by transcription factors |
| topic | Biological sciences Cellular neuroscience Biotechnology Stem cells research Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222014444 |
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