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dc.contributor.authorGhila, Luiza
dc.contributor.authorBjørlykke, Yngvild
dc.contributor.authorLegøy, Thomas Aga
dc.contributor.authorVethe, Heidrun
dc.contributor.authorFuruyama, Kenichiro
dc.contributor.authorChera, Simona
dc.contributor.authorRæder, Helge
dc.date.accessioned2021-05-11T12:01:50Z
dc.date.available2021-05-11T12:01:50Z
dc.date.created2020-09-28T16:11:00Z
dc.date.issued2020
dc.PublishedBiomedicines. 2020, 8 (7), 1-20.
dc.identifier.issn2227-9059
dc.identifier.urihttps://hdl.handle.net/11250/2754920
dc.description.abstractMutations in the hepatocyte nuclear factor 4α (HNF4α) gene affect prenatal and postnatal pancreas development, being characterized by insulin-producing β-cell dysfunction. Little is known about the cellular and molecular mechanisms leading to β-cell failure as result of HNF4α mutation. In this study, we compared the miRNA profile of differentiating human induced pluripotent stem cells (hiPSC) derived from HNF4α+/Δ mutation carriers and their family control along the differentiation timeline. Moreover, we associated this regulation with the corresponding transcriptome profile to isolate transcript–miRNA partners deregulated in the mutated cells. This study uncovered a steep difference in the miRNA regulation pattern occurring during the posterior foregut to pancreatic endoderm transition, defining early and late differentiation regulatory windows. The pathway analysis of the miRNAome–transcriptome interactions revealed a likely gradual involvement of HNF4α+/Δ mutation in p53-mediated cell cycle arrest, with consequences for the proliferation potential, survival and cell fate acquisition of the differentiating cells. The present study is based on bioinformatics approaches and we expect that, pending further experimental validation, certain miRNAs deregulated in the HNF4α+/Δ cells would prove useful for therapy.en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleBioinformatic analyses of miRNA-mRNA signature during hiPSC differentiation towards insulin-producing cells upon HNF4α mutationen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2020 The Authorsen_US
dc.source.articlenumber179en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.3390/BIOMEDICINES8070179
dc.identifier.cristin1834448
dc.source.journalBiomedicinesen_US
dc.source.408
dc.source.147
dc.identifier.citationBiomedicines. 2020, 8(7), 179en_US
dc.source.volume8en_US
dc.source.issue7en_US


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