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Article

Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons

1
Group 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, Sweden
2
Group of Regenerative Neurophysiology, Lund Stem Cell Center, Department of Experimental Medical Science, Faculty of Medicine, Lund University, 221 84 Lund, Sweden
*
Author to whom correspondence should be addressed.
Cells 2020, 9(11), 2451; https://doi.org/10.3390/cells9112451
Received: 7 October 2020 / Revised: 6 November 2020 / Accepted: 9 November 2020 / Published: 10 November 2020
(This article belongs to the Special Issue Neuron-Glia Interactions)
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. View Full-Text
Keywords: human embryonic stem cells; neurological disorders; PDGFRα; GFAP; cellular reprogramming; induced neurons; direct conversion; PV; patch-clamp electrophysiology human embryonic stem cells; neurological disorders; PDGFRα; GFAP; cellular reprogramming; induced neurons; direct conversion; PV; patch-clamp electrophysiology
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MDPI and ACS Style

Giacomoni, J.; Bruzelius, A.; Stamouli, C.-A.; Rylander Ottosson, D. Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons. Cells 2020, 9, 2451. https://doi.org/10.3390/cells9112451

AMA Style

Giacomoni J, Bruzelius A, Stamouli C-A, Rylander Ottosson D. Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons. Cells. 2020; 9(11):2451. https://doi.org/10.3390/cells9112451

Chicago/Turabian Style

Giacomoni, Jessica, Andreas Bruzelius, Christina-Anastasia Stamouli, and Daniella Rylander Ottosson. 2020. "Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons" Cells 9, no. 11: 2451. https://doi.org/10.3390/cells9112451

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