“Caspases, known as ‘killer enzymes,’ that are activated during programmed cell death, are also active in the initial phases of cell differentiation,” said Dr. Thomas Zwaka, assistant professor in the Stem Cells and Regenerative Medicine Center (STaR) at BCM.
Research into embryonic stem cells is basic to understanding differentiation, the process by which some of the earliest cells begin the process of becoming different tissues and organs. Scientists are eager to tap the potential of the pluripotent embryonic stem cells because they have the ability to become almost any kind of cell in the body. That is, however, just one of the possible fates they face. They are also capable of almost infinite self-renewal made possible by an autoregulatory loop including several key transcription factors (e.g., Oct4, Nanog). (Transcription factors bind to DNA to control the transfer of genetic information into RNA.)
The involvement of caspases in differentiation came as a surprise, said Zwaka. However, it makes a certain kind of sense.
“From a more philosophical point of view, programmed cell death (apoptosis) is a specialized form of differentiation,” said Zwaka. (Cells undergo apoptosis or programmed cell death for a variety of reasons – most of them related to keeping organisms or tissues healthy.)
In studies in his laboratory, he and his colleagues at BCM found an “overlap between the pathways that drive cell death and cell differentiation” in a group of enzymes called caspases.
“Caspases trigger differentiation,” he said. “If you remove specific caspases, stem cells have a differentiation defect. When we artificially increase caspase activity, the cells differentiated. When we increased the enzyme activity even more, the cell went into programmed cell death.”
In studying how caspases achieve this activity, he noted that the enzyme is a protease or molecular scissors that cleave or cut proteins at specific points. In particular, they found that caspase cleaves Nanog, one of the transcription factors key to maintaining the embryonic stem cells in their self-renewal state.
“This is a proof of concept study,” said Zwaka. “It shows a strong link between cell death and differentiation pathways. We hope this is a general concept that we can apply in other kinds of stem cells.”
The finding has implications for other kinds of studies. One is that manipulating programmed cell death pathways and caspase targets could help to revert a somatic or already differentiated cell into an embryonic stem cell-like fate. For instance manipulating Nanog at the caspase cleavage site might improve the effectiveness of this technique and enable elimination of the use of viruses, which can contaminate cell lines.
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The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
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Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
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In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
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