“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.
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
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23.02.2018 | Physics and Astronomy