Fang-Xu Jiang, Jing Sui, Munish Mehta and Grant Morahan
Scientific Tracks Abstracts: J Cell Sci Ther
Embryonic stem cells (ESCs), promising as a renewable source for regenerative mdicine, have yet been diff erentiated into insulin-secreting cells for a replacement therapy in type 1 diabbetes, due at least partially to the knowledge gap of transcription factors (TFs) for pancreas development. We hypothesise here that the ESCs should provide a powerful model to identify novel pancreatic TF genes at the genomic level, provided the in vivo developmental process could be recapitulated in vitro by directed diff erentiation. Guided by knowledge of their normal development and RT-PCR and immunochemical analyses, we have established protocols for directed diff erentiation of mESCs into pancreatic progenitors. Indeed at day 15, a group of pancreatic progenitor marker genes including Pdx1, Ptf1a, Nkx6.1, Pax4 and Pax6 was up- regulated. Consistently, Pdx1-immunoreactive cells were detected on day 15. Most of these Pdx1 + cells also expressed Nkx6.1. Microarray analyses of these diff erentiating ESC cells at days 0, 4, 8 and 15 confi rmed their sequential diff erentiation and our bioinformatics algorithms for sequential datasets allowed us identifi ed over 20 potential novel TF genes for pancreatic islet lineage development. Th e dynamic expression of representative known and novel genes was confi rmed by quantitative real time RT-PCR analysis. Th is strategy may be modifi ed to identify novel regulatory molecules for development of other tissue and organ systems.
Associate Prof Fang-Xu Jiang is Head of Islet Cell Development Program, The University of Western Australia. His research interest focuses mainly on proliferation, differentiation, self-renewal and regeneration of pancreatic insulin-secreting β -cell progenitors, including the molecular mechanisms of these biological processes. The ultimate aim is to generate unlimited number of β cells in vitro or stimulate patient?s own progenitor/stem cells to become β cells in vivo to cure this disease
