Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons
Glial progenitor cells are widely distributed in brain parenchyma and represent a suitable target for future therapeutic interventions that generate new neurons via in situ reprogramming. Previous studies have shown successful reprogramming of mouse glia into neurons whereas the conversion of human...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/11/2451 |
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| author | Jessica Giacomoni Andreas Bruzelius Christina-Anastasia Stamouli Daniella Rylander Ottosson |
| author_facet | Jessica Giacomoni Andreas Bruzelius Christina-Anastasia Stamouli Daniella Rylander Ottosson |
| author_sort | Jessica Giacomoni |
| collection | DOAJ |
| description | Glial progenitor cells are widely distributed in brain parenchyma and represent a suitable target for future therapeutic interventions that generate new neurons via in situ reprogramming. Previous studies have shown successful reprogramming of mouse glia into neurons whereas the conversion of human glial cells remains challenging due to the limited accessibility of human brain tissue. Here, we have used a recently developed stem cell-based model of human glia progenitor cells (hGPCs) for direct neural reprogramming by overexpressing a set of transcription factors involved in GABAergic interneuron fate specification. GABAergic interneurons play a key role in balancing excitatory and inhibitory neural circuitry in the brain and loss or dysfunction of these have been implicated in several neurological disorders such as epilepsy, schizophrenia, and autism. Our results demonstrate that hGPCs successfully convert into functional induced neurons with postsynaptic activity within a month. The induced neurons have properties of GABAergic neurons, express subtype-specific interneuron markers (e.g. parvalbumin) and exhibit a complex neuronal morphology with extensive dendritic trees. The possibility of inducing GABAergic interneurons from a renewable in vitro hGPC system could provide a foundation for the development of therapies for interneuron pathologies. |
| first_indexed | 2024-03-10T14:57:35Z |
| format | Article |
| id | doaj.art-1cb102046b71465ab82421fb2fc11c0a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:57:35Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1cb102046b71465ab82421fb2fc11c0a2023-11-20T20:25:03ZengMDPI AGCells2073-44092020-11-01911245110.3390/cells9112451Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic InterneuronsJessica Giacomoni0Andreas Bruzelius1Christina-Anastasia Stamouli2Daniella Rylander Ottosson3Group of Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center and Lund Stem Cell Center, Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, SwedenGroup of Regenerative Neurophysiology, Lund Stem Cell Center, Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, SwedenGroup of Regenerative Neurophysiology, Lund Stem Cell Center, Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, SwedenGroup of Regenerative Neurophysiology, Lund Stem Cell Center, Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, SwedenGlial progenitor cells are widely distributed in brain parenchyma and represent a suitable target for future therapeutic interventions that generate new neurons via in situ reprogramming. Previous studies have shown successful reprogramming of mouse glia into neurons whereas the conversion of human glial cells remains challenging due to the limited accessibility of human brain tissue. Here, we have used a recently developed stem cell-based model of human glia progenitor cells (hGPCs) for direct neural reprogramming by overexpressing a set of transcription factors involved in GABAergic interneuron fate specification. GABAergic interneurons play a key role in balancing excitatory and inhibitory neural circuitry in the brain and loss or dysfunction of these have been implicated in several neurological disorders such as epilepsy, schizophrenia, and autism. Our results demonstrate that hGPCs successfully convert into functional induced neurons with postsynaptic activity within a month. The induced neurons have properties of GABAergic neurons, express subtype-specific interneuron markers (e.g. parvalbumin) and exhibit a complex neuronal morphology with extensive dendritic trees. The possibility of inducing GABAergic interneurons from a renewable in vitro hGPC system could provide a foundation for the development of therapies for interneuron pathologies.https://www.mdpi.com/2073-4409/9/11/2451human embryonic stem cellsneurological disordersPDGFRαGFAPcellular reprogramminginduced neurons |
| spellingShingle | Jessica Giacomoni Andreas Bruzelius Christina-Anastasia Stamouli Daniella Rylander Ottosson Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons Cells human embryonic stem cells neurological disorders PDGFRα GFAP cellular reprogramming induced neurons |
| title | Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons |
| title_full | Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons |
| title_fullStr | Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons |
| title_full_unstemmed | Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons |
| title_short | Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons |
| title_sort | direct conversion of human stem cell derived glial progenitor cells into gabaergic interneurons |
| topic | human embryonic stem cells neurological disorders PDGFRα GFAP cellular reprogramming induced neurons |
| url | https://www.mdpi.com/2073-4409/9/11/2451 |
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