title: The combined expression of Pdx1 and MafA with either Ngn3 or NeuroD improves the differentiation efficiency of mouse embryonic stem cells into insulin-producing cells.
abstract: The use of pancreatic β-cells differentiated from embryonic stem (ES) cells or induced pluripotent stem (iPS) cells is a promising strategy in cell therapy. Pancreatic β-cell development is regulated by the sequential expression of a molecular network of transcription factors. In this experiment, we adopted a three-step differentiation protocol to differentiate mES (mouse ES) cells into insulin-secreting cells and overexpressed transcription factors by adenoviral vectors at various combinations at different time of differentiation. We found that the coexpression of Pdx1 and MafA with either Ngn3 or NeuroD, especially at the final stage of the three-step differentiation, significantly increased the differentiation efficiency. It also increased the glucose-stimulated insulin and C-peptide secretion in insulin-secreting cells derived from mES cells compared to the control green fluorescent protein (GFP) vector-transduced group. For the first time, we have demonstrated that the coexpression of Pdx1 and MafA during a specific time window of development can act synergistically with either Ngn3 or NeuroD to promote the differentiation of mES cells into insulin-secreting cells.
authors: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
authors: Huiming
authors: H
authors: Xu
authors: Kam Sze
authors: KS
authors: Tsang
authors: Juliana C N
authors: JC
authors: Chan
authors: Ping
authors: P
authors: Yuan
authors: Rongrong
authors: R
authors: Fan
authors: Hideaki
authors: H
authors: Kaneto
authors: Gang
authors: G
authors: Xu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051473:Maf Transcription Factors, Large / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D051473:Maf Transcription Factors, Large; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C485160:Mafa protein, mouse; C407737:Neurog3 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein; C093564:Neurogenic differentiation factor 1