Reprogramming human adult fibroblasts into GABAergic interneurons
Bruzelius, Andreas LU ; Kidnapillai, Srisaiyini LU ; Drouin-Ouellet, Janelle LU ; Stoker, Tom ; Barker, Roger A. LU and Ottosson, Daniella Rylander LU
(2021)
In Cells
10(12).
- Abstract
Direct reprogramming is an appealing strategy to generate neurons from a somatic cell by forced expression of transcription factors. The generated neurons can be used for both cell replacement strategies and disease modelling. Using this technique, previous studies have shown that γ-aminobutyric acid (GABA) expressing interneurons can be generated from different cell sources, such as glia cells or fetal fibroblasts. Nevertheless, the generation of neurons from adult human fibroblasts, an easily accessible cell source to obtain patient-derived neurons, has proved to be challenging due to the intrinsic blockade of neuronal commitment. In this paper, we used an optimized protocol for adult skin fibroblast reprogramming based on RE1... (More)
Direct reprogramming is an appealing strategy to generate neurons from a somatic cell by forced expression of transcription factors. The generated neurons can be used for both cell replacement strategies and disease modelling. Using this technique, previous studies have shown that γ-aminobutyric acid (GABA) expressing interneurons can be generated from different cell sources, such as glia cells or fetal fibroblasts. Nevertheless, the generation of neurons from adult human fibroblasts, an easily accessible cell source to obtain patient-derived neurons, has proved to be challenging due to the intrinsic blockade of neuronal commitment. In this paper, we used an optimized protocol for adult skin fibroblast reprogramming based on RE1 Silencing Transcription Factor (REST) inhibitn together with a combination of GABAergic fate determinants to convert human adult skin fibroblasts into GABAergic neurons. Our results show a successful conversion in 25 days with upregulation of neuronal gene and protein expression levels. Moreover, we identified specific gene combinations that converted fibroblasts into neurons of a GABAergic intraneuronal fate. Despite the well-known difficulty in converting adult fibroblasts into functional neurons in vitro, we could detect functional maturation in the induced neurons. GABAergic interneurons have relevance for cognitive impairments and brain disorders, such as Alzheimer’s and Parkinson’s diseases, epilepsy, schizophrenia and autism spectrum disorders.
(Less)
- author
- Bruzelius, Andreas
LU
; Kidnapillai, Srisaiyini
LU
; Drouin-Ouellet, Janelle
LU
; Stoker, Tom
; Barker, Roger A.
LU
and Ottosson, Daniella Rylander
LU
- organization
- publishing date
- 2021-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult skin cells, Calbindin, Direct reprogramming, Disease-modelling, Electrophysiology, IN, Neuronal conversion
- in
- Cells
- volume
- 10
- issue
- 12
- article number
- 3450
- publisher
- MDPI AG
- external identifiers
-
- scopus:85120667248
- pmid:34943958
- ISSN
- 2073-4409
- DOI
- 10.3390/cells10123450
- language
- English
- LU publication?
- yes
- id
- 273dd485-8cfc-4f11-9e23-8bf051e08ff2
- date added to LUP
- 2022-01-25 12:29:30
- date last changed
- 2024-06-16 00:21:52
@article{273dd485-8cfc-4f11-9e23-8bf051e08ff2,
abstract = {{<p>Direct reprogramming is an appealing strategy to generate neurons from a somatic cell by forced expression of transcription factors. The generated neurons can be used for both cell replacement strategies and disease modelling. Using this technique, previous studies have shown that γ-aminobutyric acid (GABA) expressing interneurons can be generated from different cell sources, such as glia cells or fetal fibroblasts. Nevertheless, the generation of neurons from adult human fibroblasts, an easily accessible cell source to obtain patient-derived neurons, has proved to be challenging due to the intrinsic blockade of neuronal commitment. In this paper, we used an optimized protocol for adult skin fibroblast reprogramming based on RE1 Silencing Transcription Factor (REST) inhibitn together with a combination of GABAergic fate determinants to convert human adult skin fibroblasts into GABAergic neurons. Our results show a successful conversion in 25 days with upregulation of neuronal gene and protein expression levels. Moreover, we identified specific gene combinations that converted fibroblasts into neurons of a GABAergic intraneuronal fate. Despite the well-known difficulty in converting adult fibroblasts into functional neurons in vitro, we could detect functional maturation in the induced neurons. GABAergic interneurons have relevance for cognitive impairments and brain disorders, such as Alzheimer’s and Parkinson’s diseases, epilepsy, schizophrenia and autism spectrum disorders.</p>}},
author = {{Bruzelius, Andreas and Kidnapillai, Srisaiyini and Drouin-Ouellet, Janelle and Stoker, Tom and Barker, Roger A. and Ottosson, Daniella Rylander}},
issn = {{2073-4409}},
keywords = {{Adult skin cells; Calbindin; Direct reprogramming; Disease-modelling; Electrophysiology; IN; Neuronal conversion}},
language = {{eng}},
number = {{12}},
publisher = {{MDPI AG}},
series = {{Cells}},
title = {{Reprogramming human adult fibroblasts into GABAergic interneurons}},
url = {{http://dx.doi.org/10.3390/cells10123450}},
doi = {{10.3390/cells10123450}},
volume = {{10}},
year = {{2021}},
}