Pharmaceutical Business review

Scientists identify gene that regulates stem cell differentiation

The gene encodes a protein that is most similar to the protein piwi, an important regulator of stem cells in organisms ranging from plants to humans.

The new study, published in the journal Science, was led by Howard Hughes Medical Institute investigator Alejandro Sanchez Alvarado.

The study found that if a piece of an adult flatworm planaria is cut off that is only 1/279th of the size of the animal, the severed piece will re-grow into a new fully functioning worm. The ability of the flatworm planaria to regenerate itself is dependent on stem cells in the adult planaria known as neoblasts. Like all stem cells, neoblasts are able to develop into a variety of different cell types, meaning they can transform themselves into whatever tissue is needed following injury.

Mr Alvarado and his colleagues set out to understand exactly how neoblasts carry out the remarkable maintenance and recreation of the varied tissues that make up a flatworm.

The scientists used RNA interference to specifically turn off the piwi gene in planaria. When they did this, they found that worms had the same defects as those whose neoblasts have been destroyed by radiation – head regression, curling, and the inability to regenerate – suggesting that the gene was needed for normal neoblast function.

When neoblasts divide, they produce at least two cell types – one copy of the original, and one cell that can develop into a specialized cell to replace a lost cell elsewhere in the body. The researchers found that without piwi, the daughter cells from this division failed to differentiate into a specialized cell once they’d reached their destination.

Based on their findings, Mr Alvarado said, “We think that piwi is actually involved in producing daughter cells that are competent to restore aged differentiated cells during homeostasis as well as missing tissues after amputation. Unlike what’s been thought about piwi for some time, which is that it was required to maintain the stem cell, we think that’s not happening here. The stem cells are being maintained by another mechanism, and it’s the division progeny, instead, that is being affected.”

There’s some evidence, he said, that piwi plays a similar role in regulating the progeny of adult stem cells in humans. He cautioned that more work is needed to determine just how functionally similar the factors regulating stem cells in planaria are to those in higher organisms. But so far there is good evidence that many of the important genes are the same, he said.