Researchers from Harvard University have developed a powerful new tool in the fight against diabetes. Currently, sixteen million Americans are afflicted with diabetes; this number is expected surpass twenty-two million by the year 2025. One approach to cure diabetes is to transplant into patients stem cells that have been specifically engineered to produce endocrine hormones. As published in Genes & Development, Dr. Doug Melton and colleagues have developed a model system to evaluate which genes can effectively drive pancreatic development, and would thus be candidates for introduction into therapeutic stem cells.
Previous research into pancreas development has utilized knockout mice to determine which genes are necessary for pancreatic development. Dr. Melton and colleagues set out to determine which genes(s) are sufficient for pancreatic development. The technique they have pioneered involves the introduction of a gene of interest, or a combination of such genes, into the endoderm of live chick embryos. The region of endoderm targeted for gene introduction is not normally fated for pancreas development. Therefore, if the introduced gene(s) is sufficient to direct pancreas development, pancreatic cell differentiation will occur ectopically.
The results have been surprising. Pdx-1, a gene that has been regarded as the pancreatic master switch, was shown to be insufficient for complete pancreatic cytodifferentiation. However, Dr. Melton and colleagues did discover that the known gene regulator, NGN3, is sufficient to cause pancreatic islet differentiation and endocrine hormone expression in non-pancreatic regions of the endoderm. These results shed new light on the role of each of these genes in pancreatic development.
The in vivo experimental system that Dr. Melton and colleagues have developed represents a fundamental tool in understanding pancreatic development and determining which genes are candidates for therapeutic usage. As diabetes kills one hundred and eighty thousand Americans each year, further delineation of the molecular mechanism underlying pancreatic development will lend insight and hope to people across the country, and throughout the world.
Genes & Development is a publication of the Cold Spring Harbor Laboratory Press.
Journal
Genes & Development