Fly Stem Cells on Diet
A study led by Salk assistant professor Leanne Jones revealed that stem cells can sense a decrease in available nutrients and respond by retaining only a small pool of active stem cells for tissue maintenance. When, or if, favorable conditions return, stem cell numbers multiply to accommodate increased demands on the tissue, her team reported in the journal Current Biology.
Elucidating the mechanisms by which hormonal signaling influences stem cell behavior under normal conditions and in response to stress provides important insights into the activities of stem cells in regenerative medicine, during wound repair, and in individuals experiencing metabolic stress.
"Tissues that are maintained by stem cells respond to adverse environmental conditions by reducing the overall number of stem cells, as well as the activity of those stem cells, but maintain them in such a state that they can respond quickly and effectively once the nutritional conditions become more favorable," says Jones.
Stem cells, with their defining characteristics—extensive proliferative potential and an ability to give rise to one or more specialized cell types—are common in early embryos. But by adulthood, only a few stem cells remain, tucked away in their own private niches. They have, nonetheless, retained a remarkable capability: they can operate at a "steady state" to maintain and repair tissues.
When food becomes scarce, animals may go through a period of reduced metabolism to allocate limited resources and maintain tissue homeostasis. In addition, a number of animals, such as those that hibernate, experience a decrease in metabolic rate as part of their normal cycle.
"But very little was known about the effect of chronic changes in metabolism on adult stem cells and the tissues that they maintain," says Jones.
To learn more, the researchers addressed the effects of nutrient availability by feeding their flies a "poor," proteinless diet for several weeks. As a result, the levels of circulating insulin-like peptides plummeted and the number of stem cells in the flies' testes and intestines started to decline. Upon re-feeding, insulin-like peptide expression and stem cell count recovered quickly.
Jones and her team think it likely that the link between hormonal signaling and stem cell response will turn out to be important not only for nutrient deprivation but also for other situations where a body's metabolism might be altered.
"One may think of how tissue homeostasis is modified in a situation when the body cannot accurately monitor or utilize available nutrients— for instance, in the case of a person who is diabetic," says Jones.
"Further investigating the relationship between nutrient availability and stem cell behavior may also lead to clues for why people who are overfed or malnourished are prone to develop metabolic diseases or cancers, in which cells fail to differentiate properly," adds postdoctoral researcher and co-first author Lei Wang, Ph.D.
An intriguing question arising from the study is whether an extreme shift in a patient's eating habits could be considered an element of a treatment.