title: Reprogramming of various cell types to a beta-like state by Pdx1, Ngn3 and MafA.
abstract: The three transcription factors, PDX1, NGN3 and MAFA, are very important in pancreatic development. Overexpression of these three factors can reprogram both pancreatic exocrine cells and SOX9-positive cells of the liver into cells resembling pancreatic beta cells. In this study we investigate whether other cell types can be reprogrammed. Eight cell types are compared and the results are consistent with the idea that reprogramming occurs to a greater degree for developmentally related cells (pancreas, liver) than for other types, such as fibroblasts. Using a line of mouse hepatocyte-derived cells we screened 13 compounds for the ability to increase the yield of reprogrammed cells. Three are active and when used in combination they can increase the yield of insulin-immunopositive cells by a factor of six. These results should contribute to the eventual ability to develop a new cure for diabetes based on the ability to reprogram other cells in the body to a beta cell phenotype.
authors: Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Ersin
authors: E
authors: Akinci
authors: Anannya
authors: A
authors: Banga
authors: Katie
authors: K
authors: Tungatt
authors: Joanna
authors: J
authors: Segal
authors: Daniel
authors: D
authors: Eberhard
authors: James R
authors: JR
authors: Dutton
authors: Jonathan M W
authors: JM
authors: Slack
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D018398:Homeodomain Proteins / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D051473:Maf Transcription Factors, Large / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000502:physiology*
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