Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule

Abstract Human pluripotent stem cells (hPSCs) play important role in studying the function of human glutamatergic neurons and related disease pathogenesis. However, the current hPSC-derived cortical system produced a significant number of inhibitory GABAergic neurons that reduced the purity of excit...

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Autores principales:	Shi-Ying Cao, Yao Hu, Cheng Chen, Fang Yuan, Min Xu, Qi Li, Kai-Heng Fang, Yaoyu Chen, Yan Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3af8a0054d549e5bf87dcd461c40c7d
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spelling	oai:doaj.org-article:f3af8a0054d549e5bf87dcd461c40c7d2021-12-02T12:30:43ZEnhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule10.1038/s41598-017-03519-w2045-2322https://doaj.org/article/f3af8a0054d549e5bf87dcd461c40c7d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03519-whttps://doaj.org/toc/2045-2322Abstract Human pluripotent stem cells (hPSCs) play important role in studying the function of human glutamatergic neurons and related disease pathogenesis. However, the current hPSC-derived cortical system produced a significant number of inhibitory GABAergic neurons that reduced the purity of excitatory neurons. In this study, we established a robust hPSC-derived cortical neurogenesis system by applying the SHH inhibitor cyclopamine. Cyclopamine specified the dorsal cortical fate in a dose-dependent manner and enhanced the generation of cortical glutamatergic neurons, expressing PAX6, TBR1, TBR2, CTIP2, SATB2, and vesicular glutamate transporters (vGLUT). In contrast, the ventral patterning was inhibited and the GABAergic neurons were significantly reduced to 12% with the treatment of cyclopamine. In addition, we applied our current method to generate trisomy 21 iPSC-derived glutamatergic neurons that showed a robust reduction of vesicular glutamate transporters in the glutamatergic neurons with trisomy 21, revealing the developmental deficits in cortical glutamatergic neurons. Our method enriched the generation of cortical glutamatergic neurons which may facilitate the study of human neurological diseases and cell therapy.Shi-Ying CaoYao HuCheng ChenFang YuanMin XuQi LiKai-Heng FangYaoyu ChenYan LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shi-Ying Cao Yao Hu Cheng Chen Fang Yuan Min Xu Qi Li Kai-Heng Fang Yaoyu Chen Yan Liu Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule
description	Abstract Human pluripotent stem cells (hPSCs) play important role in studying the function of human glutamatergic neurons and related disease pathogenesis. However, the current hPSC-derived cortical system produced a significant number of inhibitory GABAergic neurons that reduced the purity of excitatory neurons. In this study, we established a robust hPSC-derived cortical neurogenesis system by applying the SHH inhibitor cyclopamine. Cyclopamine specified the dorsal cortical fate in a dose-dependent manner and enhanced the generation of cortical glutamatergic neurons, expressing PAX6, TBR1, TBR2, CTIP2, SATB2, and vesicular glutamate transporters (vGLUT). In contrast, the ventral patterning was inhibited and the GABAergic neurons were significantly reduced to 12% with the treatment of cyclopamine. In addition, we applied our current method to generate trisomy 21 iPSC-derived glutamatergic neurons that showed a robust reduction of vesicular glutamate transporters in the glutamatergic neurons with trisomy 21, revealing the developmental deficits in cortical glutamatergic neurons. Our method enriched the generation of cortical glutamatergic neurons which may facilitate the study of human neurological diseases and cell therapy.
format	article
author	Shi-Ying Cao Yao Hu Cheng Chen Fang Yuan Min Xu Qi Li Kai-Heng Fang Yaoyu Chen Yan Liu
author_facet	Shi-Ying Cao Yao Hu Cheng Chen Fang Yuan Min Xu Qi Li Kai-Heng Fang Yaoyu Chen Yan Liu
author_sort	Shi-Ying Cao
title	Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule
title_short	Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule
title_full	Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule
title_fullStr	Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule
title_full_unstemmed	Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule
title_sort	enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f3af8a0054d549e5bf87dcd461c40c7d
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Enhanced derivation of human pluripotent stem cell-derived cortical glutamatergic neurons by a small molecule

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