In a study that could have a great impact on people with type 1 diabetes, Senta Georgia, PhD, 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.
“The field of regenerative medicine and stem cells has great potential to define new treatments that harness the body’s own developmental and restorative processes to promote healing and undo damage from chronic inflammatory or environmental injuries. The work that Dr. Georgia is pursuing is a perfect example of this new frontier in biomedical investigation and health,” said Brent Polk, MD, director of The Saban Research Institute.
Beta cells of the pancreas produce insulin. People with type 1 diabetes have a deficiency of beta cells, and therefore 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 p53 is a key target of DNMT1 in progenitor cells during embryogenesis.
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
This discovery adds a piece to the puzzle. - If you want to produce lots of insulin-producing cells from stem cells of any kind then you need to know the right signals to provide and as importantly the temporal aspects of when to provide the signals to the cells. There is a wide variety of methylases involved in controlling the epigenetic profile of a cell as it transitions from stem to differentiated cell type and the fact that they have demonstrated a role for one of these enzymes is important - it’s a piece of the overall puzzle.