Stem cell study sheds new light on disease formation

For the first time, researchers have shown that an essential biological process known as protein synthesis can be studied in adult stem cells.

The ground-breaking findings also demonstrate that the precise amount of protein produced by blood-forming stem cells is crucial to their function.

“This finding not only tells us something new about stem cell regulation but also opens up the ability to study differences in protein synthesis between many kinds of cells in the body,” said Sean Morrison, director of the children's medical centre research institute at University of Toronto.

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

Different types of blood cells produce vastly different amounts of protein per hour, and stem cells in particular synthesise 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,” Morrison added.

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 tumour-suppressor gene 'Pten' in blood-forming stem cells.

In both instances, stem cell function 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.

“Many people think of protein synthesis as a housekeeping function, in that it happens behind the scenes in all cells. The reality is that a lot of housekeeping functions are highly regulated,” explained Robert A.J. Signer, a post-doctoral research fellow in Morrison's laboratory.

Many diseases, including degenerative diseases and certain types of cancers, are associated with mutations in the machinery that makes proteins.

Discoveries such as this raise the possibility that changes in protein synthesis are necessary for the development of those diseases, said the study published in the journal Nature.