The role of Transferrin 2 and Laminin B2 in Drosophila melanogaster intestinal stem cell homeostasis and ageing

Abstract

Ageing is accompanied by many physiological changes. This is particularly evident in the intestine, where changes in gene expression, gut barrier, and microbiome pre-empt disease and eventual mortality. A wide range of research has been carried out into intestinal homeostasis and loss of homeostasis with age, and the model organism Drosophila melanogaster provides an excellent method for ageing research.
Intestinal stem cells (ISCs) have proliferative capacity and can replenish cells that are lost in the intestine because of hazards found in the lumen of the gut. Due to an increased turnover rate compared to some other tissues, the replacement of cells must be controlled tightly to prevent insufficient or excessive cell production, both of which can be fatal to the organism. Many different factors and signalling pathways contribute to the regulation of ISC proliferation, but with age, the balance between different components is lost. Therefore, understanding how intestinal homeostasis is maintained in young flies will help elucidate how this can become disrupted with age.
Stem cell division is controlled by the ISC niche, which consists of a tightly regulated microenvironment of proliferation-inducing and -restricting signals deriving from surrounding tissues such as the muscle and from other epithelial cells. More recent research has revealed that intestinal stem cells also play an active part in contributing to their own niche.
This thesis describes the effects of two proteins, Transferrin 2 and Laminin B2, that are expressed by ISCs and the non-proliferative intestinal progenitor cells called enteroblasts. Changing their expression levels in stem and progenitor cells disrupts intestinal homeostasis, but their relationship to ageing remains unclear.