HU-developed mice could help disease research

Hebrew University of Jerusalem researchers have made a scintillating discovery – they developed a new strain of mice whose dividing cells appear with a green fluorescent protein that could better explain cancers and degenerative diseases in humans.

The work, by Prof. Yuval Dor from the university’s Institute for Medical Research Israel-Canada (IMRIC) and Dr. Amir Eden from the Alexander Silberman Institute of Life Sciences, may lead to new methods of regulating human cell proliferation, which plays a key role in diseases in which specific cells do not replicate enough, and thus cause breakdown in tissues and in cancers, in which cells multiply too much.

The study, “A Transgenic Mouse Marking Live Replicating Cells Reveals In Vivo Transcriptional Program of Proliferation,” was funded by the European Union and published in the October issue of Developmental Cell.

Cells in the human body grow and multiply during body growth or during tissue regeneration after damage. However, most mature tissues require cell division only rarely. Scientists who want 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 biological material. This limits researchers’ ability to examine important cell functions, such as the active genes.

Together with colleagues in Denmark and the US, the Jerusalem researchers created a mouse strain in which replicating cells express a fluorescent protein that is destroyed once cell division is completed. In all tissues of these mice, replicating cells are labeled by the fluorescence, which allows identification and isolation of live, replicating cells directly from healthy or diseased tissue.

Using this system, HU research associate Dr. Agnes Klochendler and doctoral student Noa Weinberg-Corem 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 liver cells. 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,” the team said. “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.”

The researchers hope to develop methods for regulating cell proliferation, including the isolation and study of the rare pancreatic cells, which could lead to new approaches to multiply insulin-producing cells in the bodies of diabetics.

The mice strain 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.