Stem-cell activators switch function, repress mature cells

December 16, 2009

COLUMBUS, Ohio - In a developing animal, stem cells proliferate and differentiate to form the organs needed for life. A new study shows how a crucial step in this process happens and how a reversal of that step contributes to cancer.

The study, led by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, shows for the first time that three proteins, called E2f1, E2f2 and E2f3, play a key role in the transition stem cells make to their final, differentiated, state.

These proteins help stimulate stem cells to grow and proliferate. But once stem cells begin to differentiate into their final cell type - a cell in the retina or in the lining of the intestine, for example - the same three proteins switch function and stop them from dividing any more.

The research also shows how these proteins can switch course yet again in cells that have mutations in the retinoblastoma (Rb) gene. Mutated Rb genes occur in many types of cancer, suggesting that these E2f proteins might offer a safe and novel therapeutic target in these tumors.

The findings are published in back-to-back papers in the Dec. 17 issue of the journal Nature.

"We show that these E2fs are gene activators in stem cells but then switch to gene repressors when stem cells begin differentiating," says Gustavo Leone, associate professor of molecular virology, immunology and medical genetics at Ohio State's James Cancer Hospital and Solove Research Institute. Leone headed the first of the two Nature studies and is a co-author on the second.

"This is a very important step in the process of differentiation," Leone says. "As organs form during development, there comes a time when their growth must stop because an organ needs only a certain number of cells and no more. The switch by these proteins from activators to repressors is essential for that to happen. "Before this, there was no suspicion that these regulatory proteins had any role in differentiated cells," says Leone. "It was thought they were important only in proliferating cells like stem cells. But that's not true."

Leone and his colleagues show the function of the proteins in differentiation in mouse embryos, retinas, lenses and intestines.

They also show how the three proteins could revert back to gene activators in cancer cells and promote tumor growth in cancers with Rb mutations. "In this case, these proteins are acting abnormally relative to the surrounding tissue, so they might provide a safe therapeutic target," Leone explains. "If we can inactivate these E2fs in cancer cells, perhaps we can prevent further tumor growth without having a major affect on healthy cells."
-end-
Funding from the National Cancer Institute, the National Institute of Child Health and Human Development, and the Department of Defense supported this research.

Ohio State University Wexner Medical Center

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.