Investigator at The Saban Research Institute Discovers Key Factor Involved in Generating Insulin-Producing Beta Cells
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LOS ANGELES (April 10, 2013) In a study that could have a great impact on people with type 1 diabetes, an investigator at The Saban Research Institute of Children’s Hospital Los Angeles has discovered a key factor required for the differentiation of pancreatic insulin-producing cells. This research has been published as the cover article in the latest issue of Genes and Development.
Beta cells of the pancreas produce insulin. People with type 1 diabetes have a deficiency of beta cells, therefore they are unable to produce enough insulin to maintain normal blood glucose levels. “Regenerative medicine has the potential to cure this disease if we can devise a method for using stem cells to make new beta cells,” said Senta Georgia, PhD, who is also an assistant professor of Pediatrics at the Keck School of Medicine of the University of Southern California.
For stem cells to differentiate into specialized cells, they must go through a series of divisions. The challenge is to determine how to direct the stem cell through many intermediate states and cell divisions so that ultimately, it becomes a beta cell. Mother stem cells must pass the appropriate cellular information to the daughter stem cells for this process to occur. One way of transmitting this “cellular memory” is through DNA methylation. An enzyme, DNMT1, is known to regulate DNA methylation during cell division but its requirement for passing on cellular memory was unknown.
In this paper, Georgia has demonstrated that DNMT1 is critical for progenitor cell survival during pancreas formation in fetal development. Molecular analysis suggests that DNMT1 represses the expression of p53, a protein that acts to inhibit cell division and to activate cell death. By decreasing the amount of p53 in models that lacked DNMT1, pancreas formation was restored. This work suggests that
This discovery could be an integral part of devising a method to generate replacement beta cells from stem cells for patients with diabetes.
Link to the article: http://genesdev.cshlp.org/content/27/4/372.full
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