Saban Investigator Discovers Key Factor In Generating Insulin-Producing Beta Cells

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 pancre-atic insulin-producing cells. The 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 restora-tive processes to promote healing and undo damage from chronic inflammato-ry or environmental injuries. The work that Dr. Senta Georgia is pursuing is a perfect example of this new frontier in biomedical investigation and health,” said Brent Polk, M.D., director of the institute.

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 glu-cose 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 Georgia, PhD, and an assistant professor of pedi-atrics at USC’s Keck School of Medicine.

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 “cel-lular memory” is through DNA methylation.  An enzyme, DNMT1, is known to regulate DNA methy-lation during cell division but its requirement for passing on cel-lular memory was unknown.

In this  paper, Georgia has demonstrated that DNMT1 is critical for progenitor cell sur-vival 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 for-mation was restored.  This work suggests that p53 is a key target of DNMT1 in progenitor cells during embryogenesis.

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