UC Berkeley research shows a more dynamic role for stem cells and insulin in the intestine, a finding that could have implications for diabetes treatment.
The research, which was published in the journal Cell on Oct. 28, shows that the quantity of intestinal stem cells grows or shrinks to accommodate food, instead of maintaining a stable quantity, as scientists previously thought.
For researchers Lucy O’Brien, postdoctoral researcher, and David Bilder, associate professor of cell and developmental biology, the logic of the findings made evolutionary sense.
“If the animal can expand the size of the intestine and digest more food but then shrink when there is not as much need, it makes the animal more efficient, more physiologically fit,” O’Brien said.
The four-year-long research project, which examined the intestines of fruit flies, began somewhat by chance, she said.
One day in the lab when O’Brien needed to observe a certain genotypic mutation, there was only one slide available — one of a fly that had not been eating.
“When I opened it, its gut was so small,” O’Brien said. “I thought there’s no way this organ could have as many cells as a normal organ I’m used to looking at. That got me wondering whether the act of feeding was actually changing the makeup of the original tissue.”
Her idea diverged from the research of the time, which argued that stem cells in fruit flies divided at a reasonably constant rate, according to O’Brien.
In the lab, she began her work by observing the flies immediately after they had undergone metamorphosis and emerged as adult flies but before they had first eaten. At this point, the stem cells were mostly “inert,” according to O’Brien.
“But when I would give the flies food, I would see the stem cells come to life, and they would divide and divide and divide and divide,” O’Brien said.
O’Brien then spent a year digitally reproducing the intestines of the fruit fly and using computerized algorithms to rigorously count the 4,000 to 10,000 cells in any given fruit fly.
Here, the small size of the fruit fly helped.
“The ability to get at really fine-grain detail about individual cells in the organ makes the fruit fly such a useful animal to study,” O’Brien said.
As a biologist, O’Brien said her first thought was that insulin — which is central to regulating metabolism — would be a key factor in the response of stem cells to food.
The secreted insulin directed stem cell growth. During feeding, insulin secretions would increase, signaling intestinal growth.
In exploring the impact of insulin, O’Brien’s research has laid preliminary groundwork regarding the use of stem cells in the treatment of diabetes in humans, according to an article by Abby Sarkar, a Harvard University graduate student, and Konrad Hochedlinger, associate professor of stem cell and regenerative biology at Harvard, that accompanied the study’s publication.
Musclelike cells in the human intestines similarly secrete insulin. However, understanding the impact of those secretions is much more challenging in the context of a human versus that of a fruit fly, O’Brien said.
“The fruit fly is going to give us indications about how the equivalent process would work in the human,” O’Brien said.
O’Brien plans to continue her current work by examining involvement of muscle tissue in the secretion of insulin. She will also explore what factors limit stem cell growth.