The article appears in the May 12 issue of The Journal of Biological Chemistry.
"Our work focused on guiding stem cells, or pancreas progenitors, to differentiate into beta cells. This approach required that we increase the number of pancreas progenitors by finding the signals that cause them to proliferate. It also required that we understand the 'cues' that activate stem cells to turn into insulin-producing beta cells," says Nora Sarvetnick, Ph.D., a Scripps Research professor in the Department of Immunology.
The overall goal of this five-year study, funded by the National Institutes of Health, was to discover the roles of two proteins-BMP4 and Id-in causing proliferation or expansion of pancreatic progenitors. Hong Hua, a postdoctoral fellow in Sarvetnick's lab, was the lead author of this study.
The progression of pancreatic stem cells to beta cells is governed by the expression of key proteins, including a class of proteins called bHLH transcription factors that regulate gene expression. Ids (inhibition of differentiation factors) are a family of proteins implicated in a number of cellular processes, including cell proliferation. The major role of Id proteins is to bind to, and inhibit, the function of bHLH proteins, including those that are important in pancreas development. Therefore, Id proteins could bind to bHLH proteins in the developing pancreas and prevent them from differentiating into mature insulin-producing cells and, at the same time, cause them to proliferate.