biostudies-literatureFontcuberta-PiSunyer MEuropean Foundation for the Study of DiabetesMinistry of Economy and Competitiveness | Instituto de Salud Carlos IIIFundació la Marató de TV3Fundación DiabetesCERO256https://www.ebi.ac.uk/biostudies/studies/S-EPMC10039074biostudies-literatureUnknown6(1)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 (Communications biologyDirect reprogramming of human fibroblasts into insulin-producing cells using transcription factors.PMC10039074120230PI19/00896EFSF/JDRF/Lilly Type 1 Programme 2017Fernandez-Ruiz RPrades ERamos-Rodriguez MRamon-Azcon JAlves-Figueiredo HNovials AServitja JMBroca CGasa RTellez NGomis REnrich CVidal JGarcia-Alaman AMontserrat NFontcuberta-PiSunyer MClua LPasquali LCervantes SWojtusciszyn AfalseDirect reprogramming of human fibroblasts into insulin-producing cells using transcription factors.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 (2023-01-01T00:00:00Z2023 Mar2026-07-14T19:11:18.587Z2025-02-18T23:23:39.968ZS-EPMC100390743696431810.1038/s42003-023-04627-2