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在缺血性中风小鼠模型中，通过敲低多嘧啶序列结合蛋白1将星形胶质细胞原位直接重编程为神经元。

In situ direct reprogramming of astrocytes to neurons via polypyrimidine tract-binding protein 1 knockdown in a mouse model of ischemic stroke.

作者信息

Yuan Meng, Tang Yao, Huang Tianwen, Ke Lining, Huang En

机构信息

Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, Fuzhou, Fujian Province, China.

Department of Human Anatomy, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, China.

出版信息

Neural Regen Res. 2024 Oct 1;19(10):2240-2248. doi: 10.4103/1673-5374.390957. Epub 2023 Dec 15.

DOI:10.4103/1673-5374.390957
PMID:38488558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11034579/
Abstract

JOURNAL/nrgr/04.03/01300535-202410000-00025/figure1/v/2024-02-06T055622Z/r/image-tiff In situ direct reprogramming technology can directly convert endogenous glial cells into functional neurons in vivo for central nervous system repair. Polypyrimidine tract-binding protein 1 (PTB) knockdown has been shown to reprogram astrocytes to functional neurons in situ. In this study, we used AAV-PHP.eB-GFAP-shPTB to knockdown PTB in a mouse model of ischemic stroke induced by endothelin-1, and investigated the effects of GFAP-shPTB-mediated direct reprogramming to neurons. Our results showed that in the mouse model of ischemic stroke, PTB knockdown effectively reprogrammed GFAP-positive cells to neurons in ischemic foci, restored neural tissue structure, reduced inflammatory response, and improved behavioral function. These findings validate the effectiveness of in situ transdifferentiation of astrocytes, and suggest that the approach may be a promising strategy for stroke treatment.

摘要

《期刊》/nrgr/04.03/01300535 - 202410000 - 00025/图1/v/2024 - 02 - 06T055622Z/图像 - tiff 原位直接重编程技术可在体内将内源性神经胶质细胞直接转化为功能性神经元，用于中枢神经系统修复。已有研究表明，敲低多聚嘧啶序列结合蛋白1（PTB）可将星形胶质细胞原位重编程为功能性神经元。在本研究中，我们使用腺相关病毒（AAV） - PHP.eB - GFAP - shPTB在由内皮素 - 1诱导的缺血性中风小鼠模型中敲低PTB，并研究GFAP - shPTB介导的直接重编程为神经元的效果。我们的结果表明，在缺血性中风小鼠模型中，敲低PTB可有效地将缺血灶中GFAP阳性细胞重编程为神经元，恢复神经组织结构，减轻炎症反应，并改善行为功能。这些发现验证了星形胶质细胞原位转分化的有效性，并表明该方法可能是一种有前景的中风治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/18bfe011f674/NRR-19-2240-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/a95896efcb3f/NRR-19-2240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/54a8025e459c/NRR-19-2240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/a92fb4caaf95/NRR-19-2240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/8cd2398b48db/NRR-19-2240-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/b16cf03e7e32/NRR-19-2240-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/1581a0b8a941/NRR-19-2240-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/18bfe011f674/NRR-19-2240-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/a95896efcb3f/NRR-19-2240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/54a8025e459c/NRR-19-2240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/a92fb4caaf95/NRR-19-2240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/8cd2398b48db/NRR-19-2240-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/b16cf03e7e32/NRR-19-2240-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/1581a0b8a941/NRR-19-2240-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04a8/11034579/18bfe011f674/NRR-19-2240-g008.jpg

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3
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