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dc.contributor.authorMerlevede, Adriaan
dc.contributor.authorLegault, Emilie M.
dc.contributor.authorDrugge, Viktor
dc.contributor.authorBarker, Roger A.
dc.contributor.authorDrouin-Ouellet, Janelle
dc.contributor.authorOlariu, Victor
dc.date.accessioned2021-01-15T16:14:43Z
dc.date.available2021-01-15T16:14:43Z
dc.date.issued2021-01-15
dc.date.submitted2020-01-08
dc.identifier.others41598-021-81089-8
dc.identifier.other81089
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/316234
dc.descriptionFunder: Fonds du Québec en Recherche, Santé (FRQS)
dc.descriptionFunder: Parkinson Quebec.
dc.descriptionFunder: Lund University
dc.description.abstractAbstract: The direct reprogramming of adult skin fibroblasts to neurons is thought to be controlled by a small set of interacting gene regulators. Here, we investigate how the interaction dynamics between these regulating factors coordinate cellular decision making in direct neuronal reprogramming. We put forward a quantitative model of the governing gene regulatory system, supported by measurements of mRNA expression. We found that nPTB needs to feed back into the direct neural conversion network most likely via PTB in order to accurately capture quantitative gene interaction dynamics and correctly predict the outcome of various overexpression and knockdown experiments. This was experimentally validated by nPTB knockdown leading to successful neural conversion. We also proposed a novel analytical technique to dissect system behaviour and reveal the influence of individual factors on resulting gene expression. Overall, we demonstrate that computational analysis is a powerful tool for understanding the mechanisms of direct (neuronal) reprogramming, paving the way for future models that can help improve cell conversion strategies.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/114/2114
dc.subject/631/114
dc.subject/631/553/2699
dc.subject/631/553/2696
dc.subject/631/553/2709
dc.subject/631/553
dc.subject/631/553/2701
dc.subject/631/136/2128
dc.subject/631/532/2128
dc.subjectarticle
dc.titleA quantitative model of cellular decision making in direct neuronal reprogramming
dc.typeArticle
dc.date.updated2021-01-15T16:14:42Z
prism.issueIdentifier1
prism.publicationNameScientific Reports
prism.volume11
dc.identifier.doi10.17863/CAM.63343
dcterms.dateAccepted2021-01-01
rioxxterms.versionofrecord10.1038/s41598-021-81089-8
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2045-2322
pubs.funder-project-idUS National Institutes of Health (USPHS grant R01HL119102) (R01HL119102)


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