Type 1 diabetes mellitus affects an estimated 0,5% of the world population. Autoimmune rejection results in destruction of the insulin producing beta cells of the pancreas, leading to both acute and long term complications. Daily injection of exogenous insulin allows long term managment of the condition, but does not avoid long term complications. Reconstitution of the beta cell compartment by pancreas or cadaveric islet transplantation is heavily restricted by shortage of donor material and immune rejection issues. Any progress in obtaining large number of transplantable insulin producing cells would be a major advance towards a cure for the disease. The general objective of this proposal is to establish a method to transdifferentiate adult human cells to the beta cell phenotype by direct reprogramming by forced expression of an optimized set of pancreas specific transcription factors. The underlying experimental rationale is that sequential or combinatorial ectopic expression of transcription factors can induce recipient cells to establish a beta cell regulatory state. The experimental methodology is to clone a set of native or modified transcription factors known to be involved in pancreatic development into viral vectors and use them to transdiferentiate adult human cell types in conditions known to favor beta cell differentiation.