Researchers Discover Key to Cell Specialization

A fundamental question in biology is how a fertilized egg gives rise to many different cells in the body, such as nerve, blood and liver. By providing insight into that process, known as differentiation, the findings by the Einstein researchers are relevant to cancer, stem cell research and regenerative medicine.

The scientists studied cell differentiation in the fruit fly, Drosophila melanogaster. They found that cell specialization depends on a pair of proteins that act as super regulators of proteins that were already known—one super-regulating protein encouraging a cell to differentiate and the other trying to hold back the process.

The research was conducted by senior author Nicholas Baker, Ph.D., professor of genetics, of developmental and molecular biology, and of ophthalmology and visual sciences at Einstein, and graduate student Abhishek Bhattacharya, the paper’s lead author. They studied Helix-Loop-Helix proteins, “master-regulating” proteins that were known to play a role in the differentiation of fruit fly cells such as muscle, fat and nervous-system cells. By examining eye development in the fruit fly, they found that these master-regulating Helix-Loop-Helix proteins are in turn controlled by “super-regulating” proteins that bind with them.

Successful cell differentiation requires the presence of both master-regulating and super-regulating proteins. “If you don’t turn both of those keys, cell differentiation doesn’t work properly,” said Dr. Baker.

One of these super-regulating proteins, called E-protein Daughterless (Da), binds with Helix-Loop-Helix proteins to activate them. Da also triggers expression of a protein called Extramacrochaetae (Emc), which turns the Helix-Loop-Helix proteins off. Through this feedback-loop mechanism, Da and Emc allow Helix-Loop-Helix proteins to function during specific times during fruit-fly development to create the fly’s specialized cells.

Similar findings seem to apply to the Helix-Loop-Helix proteins that are present in human cells, where they are involved in cancer as well as in the differentiation of stem cells into specialized tissues. “We would expect that there will be people in the stem cell field that would be quite interested in what we have found,” Dr. Baker said.

The paper is titled “A network of broadly-expressed HLH genes regulates tissue-specific cell fates.” This research was supported in part by the National Institute of General Medical Sciences, part of the National Institutes of Health, and Research to Prevent Blindness.

About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation’s premier centers for research, medical education and clinical investigation. During the 2010-2011 academic year, Einstein is home to 724 M.D. students, 256 Ph.D. students, 122 students in the combined M.D./Ph.D. program, and 375 postdoctoral research fellows. The College of Medicine has 2,770 fulltime faculty members located on the main campus and at its clinical affiliates. In 2009, Einstein received more than $135 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five medical centers in the Bronx, Manhattan and Long Island – which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein – the College of Medicine runs one of the largest post-graduate medical training programs in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.einstein.yu.edu.