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Direct reprogramming of human fibroblasts into insulin-producing cells using transcription factors

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dc.contributor.author Fontcuberta-PiSunyer, Marta
dc.contributor.author García-Alamán, Ainhoa
dc.contributor.author Prades, Èlia
dc.contributor.author Téllez, Noèlia
dc.contributor.author Alves-Figueiredo, Hugo
dc.contributor.author Ramos-Rodríguez, Mireia
dc.contributor.author Enrich, Carlos
dc.contributor.author Fernandez-Ruiz, Rebeca
dc.contributor.author Cervantes, Sara
dc.contributor.author Clua, Laura
dc.contributor.author Ramón-Azcón, Javier
dc.contributor.author Broca, Christophe
dc.contributor.author Wojtusciszyn, Anne
dc.contributor.author Montserrat Pulido, Núria
dc.contributor.author Pasquali, Lorenzo
dc.contributor.author Novials, Anna
dc.contributor.author Servitja, Joan-Marc
dc.contributor.author Vidal Alaball, Josep
dc.contributor.author Gomis, Ramon
dc.contributor.author Gasa, Rosa
dc.date.accessioned 2023-06-06T06:09:29Z
dc.date.available 2023-06-06T06:09:29Z
dc.date.issued 2023
dc.identifier.citation Fontcuberta-PiSunyer M, García-Alamán A, Prades È, Téllez N, Alves-Figueiredo H, Ramos-Rodríguez M, Enrich C, Fernandez-Ruiz R, Cervantes S, Clua L, Ramón-Azcón J, Broca C, Wojtusciszyn A, Montserrat N, Pasquali L, Novials A, Servitja JM, Vidal J, Gomis R, Gasa R. Direct reprogramming of human fibroblasts into insulin-producing cells using transcription factors. Commun Biol. 2023 Mar 24;6(1):256. DOI: 10.1038/s42003-023-04627-2
dc.identifier.issn 2399-3642
dc.identifier.uri http://hdl.handle.net/10230/57043
dc.description.abstract Direct lineage reprogramming of one somatic cell into another without transitioning through a progenitor stage has emerged as a strategy to generate clinically relevant cell types. One cell type of interest is the pancreatic insulin-producing β cell whose loss and/or dysfunction leads to diabetes. To date it has been possible to create β-like cells from related endodermal cell types by forcing the expression of developmental transcription factors, but not from more distant cell lineages like fibroblasts. In light of the therapeutic benefits of choosing an accessible cell type as the cell of origin, in this study we set out to analyze the feasibility of transforming human skin fibroblasts into β-like cells. We describe how the timed-introduction of five developmental transcription factors (Neurog3, Pdx1, MafA, Pax4, and Nkx2-2) promotes conversion of fibroblasts toward a β-cell fate. Reprogrammed cells exhibit β-cell features including β-cell gene expression and glucose-responsive intracellular calcium mobilization. Moreover, reprogrammed cells display glucose-induced insulin secretion in vitro and in vivo. This work provides proof-of-concept of the capacity to make insulin-producing cells from human fibroblasts via transcription factor-mediated direct reprogramming.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Commun Biol. 2023 Mar 24;6(1):256
dc.rights © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Direct reprogramming of human fibroblasts into insulin-producing cells using transcription factors
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s42003-023-04627-2
dc.subject.keyword Diabetes
dc.subject.keyword Reprogramming
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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