Human Astrocytes Model Derived from Induced Pluripotent Stem Cells.

Nicolas Leventoux,Yuta Sato,Mitsuru Ishikawa,Hideyuki Okano,Kent Imaizumi,Hirotaka Watanabe,Satoru Morimoto,Kyoko Mashima,Takahiro Kondo,Shinichi Takahashi,Iki Sonn

doi:10.3390/cells9122680

Nicolas Leventoux, Yuta Sato + Show 9 more

Open Access

https://doi.org/10.3390/cells9122680

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Abstract

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.

Highlights

Accumulating evidence is supporting the role of astrocytes in the initiation and maintenance of neurodegenerative diseases [1,2,3,4]
We report an original protocol for generating Induced pluripotent stem cell (iPSC)-derived astrocytes and perform its validation at the cellular and functional levels
We used as starting material two control iPSC lines that were previously reported—201B7 iPSC line derived from a 36-year-old healthy female [35] and WD39 iPSC line from a

Summary

Introduction

Accumulating evidence is supporting the role of astrocytes in the initiation and maintenance of neurodegenerative diseases [1,2,3,4]. The exact contribution of astrocytes, the largest cell population in the central nervous system (CNS), to the development of neurodegenerative diseases has not been clarified due to limited accessibility to patients’ astrocytes. Human astrocytes and those of animal models exhibit essential differences in critical parameters such as the ratio of astrocytes to neurons [5], the spatial distribution and the complexity of astrocytes [6] or the molecular signatures and dominant signaling pathways [7]. The iPSC-derived astrocyte-like cells used in these

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