Cell proliferation is a key factor in degenerative diseases and cancers

Fluorescence microscopy section of the intestine. Green/yellow areas mark sites of cell proliferation. Cell nuclei marked in blue and nuclei with DNA replication marked in red. Credit: Agnes Klochendler

(Medical Xpress)—A newly-engineered strain of mice whose dividing cells express a fluorescent protein could open the door to new methods of regulating cell proliferation in humans. Cell proliferation plays a key role in degenerative diseases, in which specific cells do not replicate enough, and in cancers, in which cells replicate too much.

Cells in the human body grow and multiply during body growth or during after damage. However most mature tissues require only rare cell divisions. Scientists who wish to study these rare populations of replicating cells face a serious obstacle: most current methods for labeling and identifying replicating cells involve procedures that kill the cells and destroy sensitive . This limits the ability of scientists to examine important functions of these cells, for example the genes active in such cells.
 
To address this problem, two Hebrew University of Jerusalem researchers—Prof. Yuval Dor from the Institute for Medical Research Israel-Canada (IMRIC) and Dr. Amir Eden from the Alexander Silberman Institute of Life Sciences—together with colleagues in Denmark and the U.S., created a mouse strain in which replicating cells express a fluorescent protein which is destroyed once is completed. In all tissues of these mice, replicating cells are labeled by green fluorescence, which allows identification and isolation of live, replicating cells directly from healthy or .
 
Using this system, research associate Dr. Agnes Klochendler and PhD student Noa Weinberg-Corem at the Hebrew University were able to isolate a rare population of replicating cells from the livers of mice, and study the genes that they express compared with resting . Interestingly, they found that in replicating liver cells there is a significant decrease in the expression of genes responsible for key liver functions such as fatty acid and amino acid metabolism.
 
The research results indicate that when differentiated cells divide, they temporarily shift to a less differentiated state. This finding is important to our understanding of the difference between the two fundamental states of differentiation and proliferation in normal cells. It is also relevant for the situation in cancer, where cells are proliferating and often less differentiated.
 
In the future, the researchers hope to develop methods for regulating . For example, isolation and study of the rare replicating cells in the pancreas could lead to development of approaches to promote the proliferation and expansion of insulin-producing cells, whose loss is the hallmark of diabetes.
 
This could also be useful in other areas such as cancer and regenerative biology. By distinguishing between abnormally expressed genes in tumors and the genes associated with normal cell divisions, researchers may be able to identify cancer-specific replication markers with a potential to become new drug targets. Similarly, scientists could analyze the effects of specific drugs on the biology of replicating cells, providing important clues for regenerative medicine.
 
The study, A Transgenic Mouse Marking Live Replicating Cells Reveals In Vivo Transcriptional Program of Proliferation,  was funded by the European Union and is published in the October issue of Developmental Cell.

More information: bit.ly/T8qGY4

Related Stories

Knockout of protein prevents colon tumor formation in mice

Sep 29, 2011

A protein that regulates cell differentiation in normal tissue may play a different role in colon and breast cancer, activating proliferation of damaged cells, according to researchers at the University of Illinois at Chicago ...

Cancer stem cells generated by cancer outgrowth

Apr 02, 2009

Scientists have discovered that growing mouse skin cells in spheres can lead to generation of cells with properties of cancer stem cells, even without genetic manipulation of stem cell genes. This unexpected finding, published ...

Recommended for you

Diet affects men's and women's gut microbes differently

18 hours ago

The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a study by scientists from The University of Texas at Austin and six other institutions published ...

Researchers explore what happens when heart cells fail

19 hours ago

Through a grant from the United States-Israel Binational Science Foundation, Biomedical Engineering Associate Professor Naomi Chesler will embark upon a new collaborative research project to better understand ...

User comments