401V Poster Online - Virtual Posters
Wednesday April 06, 4:00 PM - 7:00 PM

Authors:
Karen Bellec ¹; Lynsey R Carroll ¹; Yu Yachuan ²; Rippei Hayashi ³; Julia Cordero ^1,2

Affiliations:
1) University of Glasgow; 2) CRUK Beatson Institute; 3) Australian National University

Keywords:
d. intestinal stem cells; j. other signaling pathways

Adult stem cells are essential actors in the maintenance of basal homeostasis and damage-induced regeneration in self-renewing tissues. This relies on an accurate regulation of the proliferation and differentiation of stem cells by highly conserved and coordinated signaling pathways. Consistently, disorders in signaling activity may lead to homeostasis disruption inducing age-associated tissues dysfunctions as well as a wide range of cancers.
One of the interests of our laboratory is to identify and understand the molecular mechanisms controlling and adjusting intestinal stem cell (ISCs) behavior to fit the proliferative demands of the gastrointestinal epithelium. For this, we work with the adult Drosophila intestine, an excellent model system that shares functional and structural homologies with its mammalian counterpart. Previous pioneer works shed light on multiple evolutionarily conserved signaling pathways involved in the regulation of ISCs proliferation such as Wnt signaling, JAK/STAT or EGFR signaling. Unexpectedly, the Piwi-interacting RNA pathway (PIWI pathway), known for its role in the repression of transposable elements in the germline, has also been shown to be essential for ISCs maintenance and function through the repression of transposable elements (Sousa-Victor et al., 2017).
Interestingly, we discovered that Aubergine (Aub), another component of the PIWI pathway, is specifically expressed in ISCs and required for their proliferation upon intestinal damage. The abolition of stem cell proliferation upon knockdown of other PIWI pathway components point to a canonical role of Aub in intestinal regeneration. This is consistent with our small RNA sequencing data revealing an increase of piRNA in the intestine upon damage which is abolished upon the knockdown of Aub. In the Drosophila germline, Aub interacts with the translation initiation factor eIF3 to promote target gene translation. In the intestine, this interaction is conserved: eIF3 is expressed in ISCs upon intestinal damage and the loss of Aub is associated with a decrease of eIF3C protein. In addition, the knockdown of eIF3 recapitulates the phenotypes observed upon the loss of Aub.
Altogether, our experiments reveal a new mechanism involved in the regulation of stem cell behavior. Our work bears implications for regenerative medicine, ageing and cancer research as it may lead to the identification of new therapeutic targets to prevent stem cell dysfunction.