Heparan Sulfate Maintains Tissue Homeostasis in Drosophila Adult Midgut

Abstract

Tissue homeostasis is maintained by differentiated progeny of residential stem cells. Adult stem cells constantly adjust their proliferation and differentiation rate to respond to tissue damage and stresses. However, how differentiated cells maintain tissue homeostasis still remains unclear. Here, we find that heparan sulfate (HS), a class of glycosaminoglycan (GAG) chains, protects differentiated cells to maintain intestinal homeostasis. HS depletion in enterocytes (ECs) leads to midgut homeostasis disruption, with accumulation of intestinal stem cell (ISC)-like cells and their progeny. HS-deficient ECs are prone to cell death/stress and induced the expression of cytokines and epidermal growth factors (EGFs), which in turn promote ISC proliferation and differentiation. Interestingly, HS depletion in ECs results in inactivation of Decapentaplegic (Dpp) signaling. Moreover, ectopic Dpp signaling completely rescued the defects caused by HS depletion. Taken together, these data demonstrate that HS protects ECs from ablation by Dpp signaling activation to maintain midgut homeostasis. Our results provide insight into the regulatory mechanisms of how differentiated cells contributes to tissue homeostasis control.