Stem cell study opens door to undiscovered world of biology

Mar 09, 2014
This photo shows Dr. Sean Morrison, Director of the Children's Research Institute and senior author of the study, right, and Dr. Robert A.J. Signer, a postdoctoral research fellow and the study's first author. Credit: University of Texas Southwestern Medical Center

For the first time, researchers have shown that an essential biological process known as protein synthesis can be studied in adult stem cells – something scientists have long struggled to accomplish. The groundbreaking findings from the Children's Medical Center Research Institute at UT Southwestern (CRI) also demonstrate that the precise amount of protein produced by blood-forming stem cells is crucial to their function.

The discovery, published online today in Nature, measures protein production, a process known as translation, and shows that protein synthesis is not only fundamental to how are regulated, but also is critical to their regenerative potential.

"We unveiled new areas of cellular biology that no one has seen before," said Dr. Sean Morrison, Director of the Children's Research Institute, Professor of Pediatrics, and the Mary McDermott Cook Chair in Pediatric Genetics at UT Southwestern Medical Center. "No one has ever studied protein synthesis in somatic stem cells. This finding not only tells us something new about stem cell regulation, but opens up the ability to study differences in protein synthesis between many kinds of cells in the body. We believe there is an undiscovered world of biology that allows different kinds of cells to synthesize protein at different rates and in different ways, and that those differences are important for cellular survival."

Dr. Adrian Salic's laboratory at Harvard Medical School chemically modified the antibiotic puromycin in a way that made it possible to visualize and quantify the amount of protein synthesized by within the body. Dr. Robert A.J. Signer, a postdoctoral research fellow in Dr. Morrison's laboratory and first author of the study, realized that this reagent could be adapted to measure new protein synthesis by stem cells and other cells in the blood-forming system.

What they came across was astonishing, Dr. Morrison said. The findings suggested that different types of produce vastly different amounts of protein per hour, and stem cells in particular synthesize much less protein than any other blood-forming cells.

"This result suggests that blood-forming stem cells require a lower rate of protein synthesis as compared to other blood-forming cells," said Dr. Morrison, the paper's senior author.

Researchers applied the findings to a mouse model with a genetic mutation in a component of the ribosome – the machinery that makes proteins – and the rate of protein production was reduced in stem cells by 30 percent. The scientists also increased the rate of protein synthesis by deleting the tumor suppressor gene Pten in blood-forming stem cells. In both instances, stem was noticeably impaired.

Together, these observations demonstrate that blood-forming stem cells require a highly regulated rate of protein synthesis, such that increases or decreases in that rate impair stem cell function.

"Amazingly, when the ribosomal mutant mice and the Pten mutant mice were bred together, stem cell function returned to normal, and we greatly delayed, and in some instances entirely blocked, the development of leukemia," Dr. Morrison said. "All of this happened because protein production in stem cells was returned to normal. It was as if two wrongs made a right."

Many diseases, including degenerative diseases and certain types of cancers, are associated with mutations in the machinery that makes proteins. However, why this is the case has yet to be understood. Discoveries such as this raise the possibility that changes in protein synthesis are necessary for the development of those diseases.

"Many people think of as a housekeeping function, in that it happens behind the scenes in all cells," Dr. Signer said. "The reality is that a lot of housekeeping functions are highly regulated; they have just not been studied enough to recognize the difference among cells. I think what we are seeing with this study is just the tip of the iceberg, where the process of is probably quite different in distinct cell types."

Explore further: Estrogen promotes blood-forming stem cell function

More information: Haematopoietic stem cells require a highly regulated protein synthesis rate, Nature, DOI: 10.1038/nature13035

add to favorites email to friend print save as pdf

Related Stories

Estrogen promotes blood-forming stem cell function

Jan 22, 2014

Scientists have known for years that stem cells in male and female sexual organs are regulated differently by their respective hormones. In a surprising discovery, researchers at the Children's Medical Center ...

Study identifies blood-forming stem cells' growth

Jan 25, 2012

Scientists with the new Children's Research Institute at UT Southwestern Medical Center have identified the environment in which blood-forming stem cells survive and thrive within the body, an important step toward increasing ...

Immune cells regulate blood stem cells

Feb 21, 2014

Researchers in Bern, Germany, have discovered that, during a viral infection, immune cells control the blood stem cells in the bone marrow and therefore also the body's own defences. The findings could allow ...

Recommended for you

Japanese scientist resigns over stem cell scandal

Dec 19, 2014

A researcher embroiled in a fabrication scandal that has rocked Japan's scientific establishment said Friday she would resign after failing to reproduce results of what was once billed as a ground-breaking study on ...

'Hairclip' protein mechanism explained

Dec 18, 2014

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

dedereu
not rated yet Mar 09, 2014
doi:10.1038/nature13035

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.