In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells
| Autor: | Avijite Kumer Sarkar, Takahiro Shiga, Wado Akamatsu, Yasuhiro Go, Rika Yasuhara, Yuka Abe, Kenji Mishima, Shiro Nakamura, Tomio Inoue, Shoji Tatsumoto, Hiroe Ishikawa, Kazuyoshi Baba, Yurie Hoashi, Kento Nakai, Keisuke Kotani |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Agonist Adult Patch-Clamp Techniques medicine.drug_class Science Neurogenesis Induced Pluripotent Stem Cells Action Potentials Blood Donors Stem cells Biology Transfection Article 03 medical and health sciences 0302 clinical medicine In vivo medicine Humans Receptor Serotonin 5-HT2A Receptor Induced pluripotent stem cell Promoter Regions Genetic Cells Cultured Neurons Multidisciplinary Depolarization In vitro Healthy Volunteers Cell biology Electrophysiology 030104 developmental biology Medicine Serotonin 030217 neurology & neurosurgery Neuroscience Signal Transduction |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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