Autocrine Wnt regulates the survival and genomic stability of embryonic stem cells

Unlike most cells in the body, embryonic stem cells renew themselves and can differentiate into almost any cell type. Although embryonic stem cells have been proposed to treat a myriad of human diseases, their use is fraught with the risk of the formation of noncancerous tumors called teratomas. The Wnt family of ligands promotes both the self-renewal and differentiation of embryonic stem cells. Augustin et al . either genetically ablated or overexpressed Evi, a protein that transports Wnts through the secretory pathway, in mouse embryonic stem cells, which would be expected to block or enhance the secretion of any of the Wnt family of ligands produced by these cells. Reducing Wnt secretion reduced the incidence of teratoma formation by Evi-deficient embryonic stem cells injected into mice. Furthermore, Wnt secretion ensured that proliferating embryonic stem cells segregated chromosomes properly and did not undergo apoptosis. Thus, enhancing Wnt signaling may prevent genomic instability in embryonic stem cells, which could help advance therapeutic application of stem cells.