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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.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.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.subjectCambridge Stem Cell Institute
dc.titleReprogramming Human Adult Fibroblasts into GABAergic Interneurons.
dc.publisher.departmentDepartment of Clinical Neurosciences - Sci
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]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
cam.orpheus.success2021-12-10 - Embargo set during processing via Fast-track
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International