Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons
Giacomoni, Jessica LU ; Bruzelius, Andreas LU ; Stamouli, Christina-Anastasia and Ottosson, Daniella LU
(2020)
In Cells
9(11).
p.1-17
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/f3b190b0-1094-4bbe-ac7f-46bcf3d1eb72
- author
- Giacomoni, Jessica
LU
; Bruzelius, Andreas
LU
; Stamouli, Christina-Anastasia
and Ottosson, Daniella
LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cells
- volume
- 9
- issue
- 11
- article number
- 2451
- pages
- 1 - 17
- publisher
- MDPI AG
- external identifiers
-
- pmid:33182669
- pmid:33182669
- scopus:85096081768
- ISSN
- 2073-4409
- DOI
- 10.3390/cells9112451
- language
- English
- LU publication?
- yes
- id
- f3b190b0-1094-4bbe-ac7f-46bcf3d1eb72
- date added to LUP
- 2020-11-16 09:46:27
- date last changed
- 2024-06-14 03:27:13
@article{f3b190b0-1094-4bbe-ac7f-46bcf3d1eb72,
abstract = {{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.}},
author = {{Giacomoni, Jessica and Bruzelius, Andreas and Stamouli, Christina-Anastasia and Ottosson, Daniella}},
issn = {{2073-4409}},
language = {{eng}},
number = {{11}},
pages = {{1--17}},
publisher = {{MDPI AG}},
series = {{Cells}},
title = {{Direct Conversion of Human Stem Cell-Derived Glial Progenitor Cells into GABAergic Interneurons}},
url = {{http://dx.doi.org/10.3390/cells9112451}},
doi = {{10.3390/cells9112451}},
volume = {{9}},
year = {{2020}},
}