In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells

Abstract The serotonin 5-HT2A receptor (5-HT2AR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HT2AR gene (HTR2A) variants, we have previo...

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Autores principales:	Kento Nakai, Takahiro Shiga, Rika Yasuhara, Avijite Kumer Sarkar, Yuka Abe, Shiro Nakamura, Yurie Hoashi, Keisuke Kotani, Shoji Tatsumoto, Hiroe Ishikawa, Yasuhiro Go, Tomio Inoue, Kenji Mishima, Wado Akamatsu, Kazuyoshi Baba
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ace7684b2994563aa3aab287a2d11fb
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spelling	oai:doaj.org-article:9ace7684b2994563aa3aab287a2d11fb2021-12-02T18:47:03ZIn vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells10.1038/s41598-021-95041-32045-2322https://doaj.org/article/9ace7684b2994563aa3aab287a2d11fb2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95041-3https://doaj.org/toc/2045-2322Abstract The serotonin 5-HT2A receptor (5-HT2AR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HT2AR gene (HTR2A) variants, we have previously established a protocol to induce HTR2A-expressing neurons from human-induced pluripotent stem cells (hiPSCs). Here, we investigated the maturation stages and electrophysiological properties of HTR2A-positive neurons induced from hiPSCs and constructed an HTR2A promoter-specific reporter lentivirus to label the neurons. We found that neuronal maturity increased over time and that HTR2A expression was induced at the late stage of neuronal maturation. Furthermore, we demonstrated successful labelling of the HTR2A-positive neurons, which had fluorescence and generated repetitive action potentials in response to depolarizing currents and an inward current during the application of TCB-2, a selective agonist of 5-HT2ARs, respectively. These results indicated that our in vitro model mimicked the in vivo dynamics of 5-HT2AR. Therefore, in vitro monitoring of the function of HTR2A-positive neurons induced from hiPSCs could help elucidate the pathophysiological mechanisms of neurological diseases associated with genetic variations of the HTR2A gene.Kento NakaiTakahiro ShigaRika YasuharaAvijite Kumer SarkarYuka AbeShiro NakamuraYurie HoashiKeisuke KotaniShoji TatsumotoHiroe IshikawaYasuhiro GoTomio InoueKenji MishimaWado AkamatsuKazuyoshi BabaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kento Nakai Takahiro Shiga Rika Yasuhara Avijite Kumer Sarkar Yuka Abe Shiro Nakamura Yurie Hoashi Keisuke Kotani Shoji Tatsumoto Hiroe Ishikawa Yasuhiro Go Tomio Inoue Kenji Mishima Wado Akamatsu Kazuyoshi Baba In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells
description	Abstract The serotonin 5-HT2A receptor (5-HT2AR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HT2AR gene (HTR2A) variants, we have previously established a protocol to induce HTR2A-expressing neurons from human-induced pluripotent stem cells (hiPSCs). Here, we investigated the maturation stages and electrophysiological properties of HTR2A-positive neurons induced from hiPSCs and constructed an HTR2A promoter-specific reporter lentivirus to label the neurons. We found that neuronal maturity increased over time and that HTR2A expression was induced at the late stage of neuronal maturation. Furthermore, we demonstrated successful labelling of the HTR2A-positive neurons, which had fluorescence and generated repetitive action potentials in response to depolarizing currents and an inward current during the application of TCB-2, a selective agonist of 5-HT2ARs, respectively. These results indicated that our in vitro model mimicked the in vivo dynamics of 5-HT2AR. Therefore, in vitro monitoring of the function of HTR2A-positive neurons induced from hiPSCs could help elucidate the pathophysiological mechanisms of neurological diseases associated with genetic variations of the HTR2A gene.
format	article
author	Kento Nakai Takahiro Shiga Rika Yasuhara Avijite Kumer Sarkar Yuka Abe Shiro Nakamura Yurie Hoashi Keisuke Kotani Shoji Tatsumoto Hiroe Ishikawa Yasuhiro Go Tomio Inoue Kenji Mishima Wado Akamatsu Kazuyoshi Baba
author_facet	Kento Nakai Takahiro Shiga Rika Yasuhara Avijite Kumer Sarkar Yuka Abe Shiro Nakamura Yurie Hoashi Keisuke Kotani Shoji Tatsumoto Hiroe Ishikawa Yasuhiro Go Tomio Inoue Kenji Mishima Wado Akamatsu Kazuyoshi Baba
author_sort	Kento Nakai
title	In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells
title_short	In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells
title_full	In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells
title_fullStr	In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells
title_full_unstemmed	In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells
title_sort	in vitro monitoring of htr2a-positive neurons derived from human-induced pluripotent stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9ace7684b2994563aa3aab287a2d11fb
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In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells

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