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.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.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.doi http://dx.doi.org/10.1038/s42003-023-04627-2
• dc.identifier.issn 2399-3642
• dc.identifier.uri http://hdl.handle.net/10230/57043
• 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.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Diabetes
• dc.subject.keyword Reprogramming
• dc.title Direct reprogramming of human fibroblasts into insulin-producing cells using transcription factors
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion