Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke
Abstract Human cortical neural progenitor cell transplantation holds significant potential in cortical stroke treatment by replacing lost cortical neurons and repairing damaged brain circuits. However, commonly utilized human cortical neural progenitors are limited in yield a substantial proportion...
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60187-5 |
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| author | Xiao He Jiadong Chen Yan Zhong Peili Cen Li Shen Fei Huang Jing Wang Chentao Jin Rui Zhou Xiaohui Zhang Anxin Wang Jing Fan Shuang Wu Mengjiao Tu Xiyi Qin Xiaoyun Luo Yu Zhou Jieqiao Peng Youyou Zhou A. Cahid Civelek Mei Tian Hong Zhang |
| author_facet | Xiao He Jiadong Chen Yan Zhong Peili Cen Li Shen Fei Huang Jing Wang Chentao Jin Rui Zhou Xiaohui Zhang Anxin Wang Jing Fan Shuang Wu Mengjiao Tu Xiyi Qin Xiaoyun Luo Yu Zhou Jieqiao Peng Youyou Zhou A. Cahid Civelek Mei Tian Hong Zhang |
| author_sort | Xiao He |
| collection | DOAJ |
| description | Abstract Human cortical neural progenitor cell transplantation holds significant potential in cortical stroke treatment by replacing lost cortical neurons and repairing damaged brain circuits. However, commonly utilized human cortical neural progenitors are limited in yield a substantial proportion of diverse cortical neurons and require an extended period to achieve functional maturation and synaptic integration, thereby potentially diminishing the optimal therapeutic benefits of cell transplantation for cortical stroke. Here, we generated forkhead box G1 (FOXG1)-positive forebrain progenitors from human inducible pluripotent stem cells, which can differentiate into diverse and balanced cortical neurons including upper- and deep-layer excitatory and inhibitory neurons, achieving early functional maturation simultaneously in vitro. Furthermore, these FOXG1 forebrain progenitor cells demonstrate robust cortical neuronal differentiation, rapid functional maturation and efficient synaptic integration after transplantation into the sensory cortex of stroke-injured adult rats. Notably, we have successfully utilized the non-invasive 18F-SynVesT-1 PET imaging technique to assess alterations in synapse count before and after transplantation therapy of FOXG1 progenitors in vivo. Moreover, the transplanted FOXG1 progenitors improve sensory and motor function recovery following stroke. These findings provide systematic and compelling evidence for the suitability of these FOXG1 progenitors for neuronal replacement in ischemic cortical stroke. |
| format | Article |
| id | doaj-art-daa06bd7e7d84b0db2cc3db5eea64977 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-daa06bd7e7d84b0db2cc3db5eea649772025-08-20T02:30:42ZengNature PortfolioNature Communications2041-17232025-06-0116112510.1038/s41467-025-60187-5Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic strokeXiao He0Jiadong Chen1Yan Zhong2Peili Cen3Li Shen4Fei Huang5Jing Wang6Chentao Jin7Rui Zhou8Xiaohui Zhang9Anxin Wang10Jing Fan11Shuang Wu12Mengjiao Tu13Xiyi Qin14Xiaoyun Luo15Yu Zhou16Jieqiao Peng17Youyou Zhou18A. Cahid Civelek19Mei Tian20Hong Zhang21Department of Nuclear Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of SciencesDepartment of Neurobiology, Departments of Neurosurgery and Neurology of the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineThe MOE Key Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang UniversityThe MOE Key Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang UniversityDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineHopstem Bioengineering Co., Ltd.Hopstem Bioengineering Co., Ltd.Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Neurobiology, Departments of Neurosurgery and Neurology of the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Neurobiology, Departments of Neurosurgery and Neurology of the Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Radiology and Radiological Science, Johns Hopkins MedicineDepartment of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Nuclear Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of SciencesAbstract Human cortical neural progenitor cell transplantation holds significant potential in cortical stroke treatment by replacing lost cortical neurons and repairing damaged brain circuits. However, commonly utilized human cortical neural progenitors are limited in yield a substantial proportion of diverse cortical neurons and require an extended period to achieve functional maturation and synaptic integration, thereby potentially diminishing the optimal therapeutic benefits of cell transplantation for cortical stroke. Here, we generated forkhead box G1 (FOXG1)-positive forebrain progenitors from human inducible pluripotent stem cells, which can differentiate into diverse and balanced cortical neurons including upper- and deep-layer excitatory and inhibitory neurons, achieving early functional maturation simultaneously in vitro. Furthermore, these FOXG1 forebrain progenitor cells demonstrate robust cortical neuronal differentiation, rapid functional maturation and efficient synaptic integration after transplantation into the sensory cortex of stroke-injured adult rats. Notably, we have successfully utilized the non-invasive 18F-SynVesT-1 PET imaging technique to assess alterations in synapse count before and after transplantation therapy of FOXG1 progenitors in vivo. Moreover, the transplanted FOXG1 progenitors improve sensory and motor function recovery following stroke. These findings provide systematic and compelling evidence for the suitability of these FOXG1 progenitors for neuronal replacement in ischemic cortical stroke.https://doi.org/10.1038/s41467-025-60187-5 |
| spellingShingle | Xiao He Jiadong Chen Yan Zhong Peili Cen Li Shen Fei Huang Jing Wang Chentao Jin Rui Zhou Xiaohui Zhang Anxin Wang Jing Fan Shuang Wu Mengjiao Tu Xiyi Qin Xiaoyun Luo Yu Zhou Jieqiao Peng Youyou Zhou A. Cahid Civelek Mei Tian Hong Zhang Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke Nature Communications |
| title | Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke |
| title_full | Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke |
| title_fullStr | Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke |
| title_full_unstemmed | Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke |
| title_short | Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke |
| title_sort | forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke |
| url | https://doi.org/10.1038/s41467-025-60187-5 |
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