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dc.contributor.authorBruzelius, Andreas
dc.contributor.authorKidnapillai, Srisaiyini
dc.contributor.authorDrouin-Ouellet, Janelle
dc.contributor.authorStoker, Tom
dc.contributor.authorBarker, Roger
dc.contributor.authorRylander Ottosson, Daniella
dc.date.accessioned2022-01-04T13:28:57Z
dc.date.available2022-01-04T13:28:57Z
dc.date.issued2021-12-08
dc.identifier.issn2073-4409
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331875
dc.description.abstractDirect 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) inhibition 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 interneuronal 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.
dc.languageen
dc.publisherMDPI AG
dc.subjectdirect reprogramming
dc.subjectelectrophysiology
dc.subjectiN
dc.subjectcalbindin
dc.subjectadult skin cells
dc.subjectneuronal conversion
dc.subjectdisease-modelling
dc.titleReprogramming Human Adult Fibroblasts into GABAergic Interneurons.
dc.typeArticle
dc.date.updated2022-01-04T13:28:56Z
prism.issueIdentifier12
prism.publicationNameCells
prism.volume10
dc.identifier.doi10.17863/CAM.79325
dcterms.dateAccepted2021-12-04
rioxxterms.versionofrecord10.3390/cells10123450
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBruzelius, Andreas [0000-0002-7175-3590]
dc.contributor.orcidStoker, Tom [0000-0001-5186-7630]
dc.contributor.orcidBarker, Roger [0000-0001-8843-7730]
dc.contributor.orcidRylander Ottosson, Daniella [0000-0002-9270-3576]
dc.identifier.eissn2073-4409
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
cam.issuedOnline2021-12-08


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