Gut stem cells

The cells that line the gut of multicellular organisms, from flies to humans, need to constantly renew themselves. In addition to toxins and harmful components that may be present in the food we eat, there’s also the microbes that co-exist with us in our guts and can sometimes do more harm than good. As a result, the epithelial cells that line our guts are under constant attack, and need to be frequently replaced.

gut stem cells

That’s the job of intestinal stem cells (or ISCs). In the fruit fly Drosophila melanogaster, ISCs divide
asymmetrically to make a new copy of themselves and a sister called enteroblast (or EB). The EB then differentiates into a large cell called enterocyte (or EC), which is in charge of absorbing nutrients from the food, or a much smaller secretory cell called enteroendocrine cell (or EE), which is in charge of secreting hormones that will regulate intestinal function and coordinate digestion with the rest of the animal’s physiology.

In the lab we use ISCs as a model to understand not only how stem cells decide whether to make a new copy of themselves or differentiate, but also how differentiating progenitors decide among alternative fates.

gut if

Intestines from flies with lower expression of Esg (esgRNAi) and the corresponding controls, which show a reduced number of ISCs (GFP+ cells) and an accumulation of Pros+ EE cells.

 

 

The reasearch that Dr. Loza-Coll did as a postdoc in the laboratory of Prof. Leanne Jones, at the Salk Institute and UCLA, demonstrated that a transcription factor called Escargot (Esg) is a critical regulator of both the self-renewal of ISCs and their fate choice between ECs and EE. More specifically, his work showed that mutating Esg in ISCs led to a spontaneous differentiation of those ISCs and, in addition, biased their fate choice towards EE cells. Notably, work by a group of
researchers led by Dr. Helen Abud at Monash University in Australia demonstrated that one of the homologues of Esg in mammals, called Snail 1, plays a very similar role in intestinal stem cells of a mouse gut, which indicates that the role of these Snail factors in the regulation of ISCs may have been conserved throughout evolution. This makes our Drosophila much more attractive as a model to understand the function of intestinal stem cells under both normal conditions and
disease.