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
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
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.
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
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.
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