دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Direct reprogramming of human fibroblasts into insulin-producing cells using transcription factors
المؤلفون: Fontcuberta-PiSunyer, Marta, García-Alamán, Ainhoa, Prades, Èlia, Téllez, Noèlia, Alves-Figueiredo, Hugo, Ramos-Rodríguez, Mireia, Enrich, Carlos, Fernandez-Ruiz, Rebeca, Cervantes, Sara, Clua, Laura, Ramón-Azcón, Javier, Broca, Christophe, Wojtusciszyn, Anne, Montserrat, Nuria, Pasquali, Lorenzo, Novials, Anna, Servitja, Joan-Marc, Vidal, Josep, Gomis, Ramon, Gasa, Rosa
المساهمون: Ministry of Economy and Competitiveness | Instituto de Salud Carlos III, Fundació la Marató de TV3, European Foundation for the Study of Diabetes, Fundación DiabetesCERO
المصدر: Communications Biology ; volume 6, issue 1 ; ISSN 2399-3642
بيانات النشر: Springer Science and Business Media LLC
سنة النشر: 2023
مصطلحات موضوعية: General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous)
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1038/s42003-023-04627-2
الإتاحة: https://doi.org/10.1038/s42003-023-04627-2Test
https://www.nature.com/articles/s42003-023-04627-2.pdfTest
https://www.nature.com/articles/s42003-023-04627-2Test
حقوق: https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test
رقم الانضمام: edsbas.40DA9AF4
قاعدة البيانات: BASE