Generation of region-specific and high-purity neurons from human feeder-free iPSCs.
Neurosci Lett
; 746: 135676, 2021 02 16.
Article
em En
| MEDLINE
| ID: mdl-33516803
ABSTRACT
Human induced pluripotent stem cells (iPSCs) have great potential to elucidate the molecular pathogenesis of neurological/psychiatric diseases. In particular, neurological/psychiatric diseases often display brain region-specific symptoms, and the technology for generating region-specific neural cells from iPSCs has been established for detailed modeling of neurological/psychiatric disease phenotypes in vitro. On the other hand, recent advances in culturing human iPSCs without feeder cells have enabled highly efficient and reproducible neural induction. However, conventional regional control technologies have mainly been developed based on on-feeder iPSCs, and these methods are difficult to apply to feeder-free (ff) iPSC cultures. In this study, we established a novel culture system to generate region-specific neural cells from human ff-iPSCs. This system is the best optimized approach for feeder-free iPSC culture and generates specific neuronal subtypes with high purity and functionality, including forebrain cortical neurons, forebrain interneurons, midbrain dopaminergic neurons, and spinal motor neurons. In addition, the temporal patterning of cortical neuron layer specification in the forebrain was reproduced in our culture system, which enables the generation of layer-specific cortical neurons. Neuronal activity was demonstrated in the present culture system by using multiple electrode array and calcium imaging. Collectively, our ff-iPSC-based culture system would provide a desirable platform for modeling various types of neurological/psychiatric disease phenotypes.
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MEDLINE
Assunto principal:
Diferenciação Celular
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Técnicas de Cultura de Células
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Células-Tronco Pluripotentes Induzidas
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Neurônios
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article