Human Astrocytes Model Derived from Induced Pluripotent Stem Cells

Induced pluripotent stem cell (iPSC)-based disease modeling has a great potential for uncovering the mechanisms of pathogenesis, especially in the case of neurodegenerative diseases where disease-susceptible cells can usually not be obtained from patients. So far, the iPSC-based modeling of neurodeg...

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Main Authors: Nicolas Leventoux, Satoru Morimoto, Kent Imaizumi, Yuta Sato, Shinichi Takahashi, Kyoko Mashima, Mitsuru Ishikawa, Iki Sonn, Takahiro Kondo, Hirotaka Watanabe, Hideyuki Okano
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/9/12/2680
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author Nicolas Leventoux
Satoru Morimoto
Kent Imaizumi
Yuta Sato
Shinichi Takahashi
Kyoko Mashima
Mitsuru Ishikawa
Iki Sonn
Takahiro Kondo
Hirotaka Watanabe
Hideyuki Okano
author_facet Nicolas Leventoux
Satoru Morimoto
Kent Imaizumi
Yuta Sato
Shinichi Takahashi
Kyoko Mashima
Mitsuru Ishikawa
Iki Sonn
Takahiro Kondo
Hirotaka Watanabe
Hideyuki Okano
author_sort Nicolas Leventoux
collection DOAJ
description Induced pluripotent stem cell (iPSC)-based disease modeling has a great potential for uncovering the mechanisms of pathogenesis, especially in the case of neurodegenerative diseases where disease-susceptible cells can usually not be obtained from patients. So far, the iPSC-based modeling of neurodegenerative diseases has mainly focused on neurons because the protocols for generating astrocytes from iPSCs have not been fully established. The growing evidence of astrocytes’ contribution to neurodegenerative diseases has underscored the lack of iPSC-derived astrocyte models. In the present study, we established a protocol to efficiently generate iPSC-derived astrocytes (iPasts), which were further characterized by RNA and protein expression profiles as well as functional assays. iPasts exhibited calcium dynamics and glutamate uptake activity comparable to human primary astrocytes. Moreover, when co-cultured with neurons, iPasts enhanced neuronal synaptic maturation. Our protocol can be used for modeling astrocyte-related disease phenotypes in vitro and further exploring the contribution of astrocytes to neurodegenerative diseases.
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spelling doaj.art-ae463b76d0b249f1b2b5e5ca963849362023-11-21T00:38:16ZengMDPI AGCells2073-44092020-12-01912268010.3390/cells9122680Human Astrocytes Model Derived from Induced Pluripotent Stem CellsNicolas Leventoux0Satoru Morimoto1Kent Imaizumi2Yuta Sato3Shinichi Takahashi4Kyoko Mashima5Mitsuru Ishikawa6Iki Sonn7Takahiro Kondo8Hirotaka Watanabe9Hideyuki Okano10Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanKeio University Graduate School of Science and Technology, Kanagawa 223-8522, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, Tokyo 160-8582, JapanInduced pluripotent stem cell (iPSC)-based disease modeling has a great potential for uncovering the mechanisms of pathogenesis, especially in the case of neurodegenerative diseases where disease-susceptible cells can usually not be obtained from patients. So far, the iPSC-based modeling of neurodegenerative diseases has mainly focused on neurons because the protocols for generating astrocytes from iPSCs have not been fully established. The growing evidence of astrocytes’ contribution to neurodegenerative diseases has underscored the lack of iPSC-derived astrocyte models. In the present study, we established a protocol to efficiently generate iPSC-derived astrocytes (iPasts), which were further characterized by RNA and protein expression profiles as well as functional assays. iPasts exhibited calcium dynamics and glutamate uptake activity comparable to human primary astrocytes. Moreover, when co-cultured with neurons, iPasts enhanced neuronal synaptic maturation. Our protocol can be used for modeling astrocyte-related disease phenotypes in vitro and further exploring the contribution of astrocytes to neurodegenerative diseases.https://www.mdpi.com/2073-4409/9/12/2680astrocytesiPSCcell culturedisease modelingneurodegenerative diseases
spellingShingle Nicolas Leventoux
Satoru Morimoto
Kent Imaizumi
Yuta Sato
Shinichi Takahashi
Kyoko Mashima
Mitsuru Ishikawa
Iki Sonn
Takahiro Kondo
Hirotaka Watanabe
Hideyuki Okano
Human Astrocytes Model Derived from Induced Pluripotent Stem Cells
Cells
astrocytes
iPSC
cell culture
disease modeling
neurodegenerative diseases
title Human Astrocytes Model Derived from Induced Pluripotent Stem Cells
title_full Human Astrocytes Model Derived from Induced Pluripotent Stem Cells
title_fullStr Human Astrocytes Model Derived from Induced Pluripotent Stem Cells
title_full_unstemmed Human Astrocytes Model Derived from Induced Pluripotent Stem Cells
title_short Human Astrocytes Model Derived from Induced Pluripotent Stem Cells
title_sort human astrocytes model derived from induced pluripotent stem cells
topic astrocytes
iPSC
cell culture
disease modeling
neurodegenerative diseases
url https://www.mdpi.com/2073-4409/9/12/2680
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