Enzyme plays key role in cell fate

June 4, 2008

The road to death or differentiation follows a similar course in embryonic stem cells, said researchers at Baylor College of Medicine in Houston in a report that appears online today in the journal Cell Stem Cell.

“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.

Source: Baylor College of Medicine

Explore further: Reprogramming the oocyte

Related Stories

Reprogramming the oocyte

August 26, 2015

(Phys.org)—Among other things, the egg is optimized to processes the sperm genome. The cytoplasmic factors that make this possible also give the egg the ability to reprogram the nuclei from other kinds of cells if these ...

Scientists develop method for discovering rare cells

August 21, 2015

Scientists of the Hubrecht Institute Utrecht developed a new method for identifying rare cell types by single-cell mRNA sequencing. The newly developed algorithm, called RaceID, is very useful for identifying rare cell types ...

Making bone in the lab

August 20, 2015

Every year there are around 60,000 hip, 50,000 forearm and 40,000 vertebral fractures in the UK. At the Bone and Joint Research Group at the University of Southampton, Professor Richard Oreffo and team have made pioneering ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.