|Tuesday September 21, 2010, from 12.00 to 13.00, Point Centre, Auditorium Albert Claude|
Patrick Collombat, Université de Nice, INSERMU636, Diabetes Genetics Team, Nice, France
(this seminar will be followed by a lunch from 13.00 to 14.00)
"In vivo reprogramming of pancreatic cells into insulin-producing beta-cells "
We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. In an effort to gain further insights into the function of Pax4, we conditionally and ectopically express this gene using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature α-cells, to adopt a β-cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3. However, the newly formed α-cells fail to correct the hypoglucagonemia as they subsequently acquire a β-cell phenotype upon Pax4 ectopic expression. Notably, this cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in α-cells is capable of restoring a functional β-cell mass and curing diabetes in animals that have been chemically depleted of β-cells.