A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical Interneurons
GABAergic interneurons control the neural circuitry and network activity in the brain. The dysfunction of cortical interneurons, especially those derived from the medial ganglionic eminence, contributes to neurological disease states. Pluripotent stem cell-derived interneurons provide a powerful too...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/5/853 |
| _version_ | 1797475410915622912 |
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| author | Maria Cruz-Santos Lucia Fernandez Cardo Meng Li |
| author_facet | Maria Cruz-Santos Lucia Fernandez Cardo Meng Li |
| author_sort | Maria Cruz-Santos |
| collection | DOAJ |
| description | GABAergic interneurons control the neural circuitry and network activity in the brain. The dysfunction of cortical interneurons, especially those derived from the medial ganglionic eminence, contributes to neurological disease states. Pluripotent stem cell-derived interneurons provide a powerful tool for understanding the etiology of neuropsychiatric disorders, as well as having the potential to be used as medicine in cell therapy for neurological conditions such as epilepsy. Although large numbers of interneuron progenitors can be readily induced in vitro, the generation of defined interneuron subtypes remains inefficient. Using CRISPR/Cas9-assisted homologous recombination in hPSCs, we inserted the coding sequence of mEmerald and mCherry fluorescence protein, respectively, downstream that of the <i>LHX6</i>, a gene required for, and a marker of medial ganglionic eminence (MGE)-derived cortical interneurons. Upon differentiation of the LHX6-mEmerald and LHX6-mCherry hPSCs towards the MGE fate, both reporters exhibited restricted expression in LHX6<sup>+</sup> MGE derivatives of hPSCs. Moreover, the reporter expression responded to changes of interneuron inductive cues. Thus, the LHX6-reporter lines represent a valuable tool to identify molecules controlling human interneuron development and design better interneuron differentiation protocols as well as for studying risk genes associated with interneuronopathies. |
| first_indexed | 2024-03-09T20:43:48Z |
| format | Article |
| id | doaj.art-81024beca7de4c50958e525fa2c6259d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:43:48Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-81024beca7de4c50958e525fa2c6259d2023-11-23T22:51:16ZengMDPI AGCells2073-44092022-03-0111585310.3390/cells11050853A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical InterneuronsMaria Cruz-Santos0Lucia Fernandez Cardo1Meng Li2Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UKNeuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UKNeuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UKGABAergic interneurons control the neural circuitry and network activity in the brain. The dysfunction of cortical interneurons, especially those derived from the medial ganglionic eminence, contributes to neurological disease states. Pluripotent stem cell-derived interneurons provide a powerful tool for understanding the etiology of neuropsychiatric disorders, as well as having the potential to be used as medicine in cell therapy for neurological conditions such as epilepsy. Although large numbers of interneuron progenitors can be readily induced in vitro, the generation of defined interneuron subtypes remains inefficient. Using CRISPR/Cas9-assisted homologous recombination in hPSCs, we inserted the coding sequence of mEmerald and mCherry fluorescence protein, respectively, downstream that of the <i>LHX6</i>, a gene required for, and a marker of medial ganglionic eminence (MGE)-derived cortical interneurons. Upon differentiation of the LHX6-mEmerald and LHX6-mCherry hPSCs towards the MGE fate, both reporters exhibited restricted expression in LHX6<sup>+</sup> MGE derivatives of hPSCs. Moreover, the reporter expression responded to changes of interneuron inductive cues. Thus, the LHX6-reporter lines represent a valuable tool to identify molecules controlling human interneuron development and design better interneuron differentiation protocols as well as for studying risk genes associated with interneuronopathies.https://www.mdpi.com/2073-4409/11/5/853CRISPR/Cas9genome editinghuman pluripotent stem cellin vitro differentiationGABAinterneuron |
| spellingShingle | Maria Cruz-Santos Lucia Fernandez Cardo Meng Li A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical Interneurons Cells CRISPR/Cas9 genome editing human pluripotent stem cell in vitro differentiation GABA interneuron |
| title | A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical Interneurons |
| title_full | A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical Interneurons |
| title_fullStr | A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical Interneurons |
| title_full_unstemmed | A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical Interneurons |
| title_short | A Novel LHX6 Reporter Cell Line for Tracking Human iPSC-Derived Cortical Interneurons |
| title_sort | novel lhx6 reporter cell line for tracking human ipsc derived cortical interneurons |
| topic | CRISPR/Cas9 genome editing human pluripotent stem cell in vitro differentiation GABA interneuron |
| url | https://www.mdpi.com/2073-4409/11/5/853 |
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