372B Poster - 04. Stem cells, regeneration and tissue injury
Friday April 08, 2:00 PM - 4:00 PM

Activin signaling controls ISC proliferation and cell fate to maintain adult gut homeostasis


Authors:
Christian Christensen; Julien Colombani; Ditte Andersen

Affiliation: University of Copenhagen, Department of Biology

Keywords:
d. intestinal stem cells; c. TGFbeta

The intestinal tract is the most proliferative organ in the body, and coordination of intestinal stem cell (ISC) activity and cell fate is dynamically tuned to ensure epithelial integrity at homeostasis and in response to injury. To identify niche-derived signals controlling adult gut homeostasis, we recently carried out a large-scale functional genetic screen using RNAis targeting secreted peptides expressed in the ISC niche. Our screen identified several of the evolutionarily conserved TGF-beta/activin ligands suggesting an important function of activin signaling in controlling gut homeostasis. Consistent with this, we found that niche-derived activin-beta signals through the type I activin receptor, baboon, in the stem- and progenitor cells to promote regenerative growth in response to an oral Ecc15 infection. Additionally, we find that activin signaling in intestinal stem- and progenitor cells participate in coordinating proliferation and cell fate decisions during homeostasis to restrict gut epithelial turnover rates and ensure gut integrity. Activin signaling was recently reported to regulate salivary gland stem/progenitor cell function in mice, suggesting a conserved role of activins in controlling adult stem cell activity and tissue homeostasis.